US Pat. No. 9,326,945

APIXABAN FORMULATIONS

Bristol-Myers Squibb Comp...

1. A solid pharmaceutical composition comprising a therapeutically effective amount of crystalline apixaban particles and
a pharmaceutically acceptable diluent or carrier,
wherein the crystalline apixaban particles have a D90 equal to or less than about 89 ?m, and

wherein at least 77 wt % of apixaban dissolves within 30 minutes in a pH 6.8 phosphate buffer containing 0.05% sodium lauryl
sulfate.

US Pat. No. 9,221,915

HUMAN MONOCLONAL ANTIBODIES TO ACTIVIN RECEPTOR-LIKE KINASE-1

Pfizer Inc., New York, N...

1. A method for treating cancer in a human in need thereof, comprising the step of administering to said human an anti-activin
receptor-like kinase-1 (ALK-1) antibody or an antigen-binding portion thereof, wherein said antibody comprises the heavy chain
CDR1-3 and the light chain CDR1-3 found in the following amino acid sequences, respectively:
a) SEQ ID NO: 6 and SEQ ID NO: 8;
b) SEQ ID NO: 14 and SEQ ID NO: 16;
c) SEQ ID NO: 18 and SEQ ID NO: 20;
d) SEQ ID NO: 26 and SEQ ID NO: 28;
e) SEQ ID NO: 30 and SEQ ID NO: 32;
f) SEQ ID NO: 38 and SEQ ID NO: 40;
g) SEQ ID NO: 46 and SEQ ID NO: 48;
h) SEQ ID NO: 50 and SEQ ID NO: 52;
i) SEQ ID NO: 54 and SEQ ID NO: 56;
j) SEQ ID NO: 58 and SEQ ID NO: 60;
k) SEQ ID NO: 62 and SEQ ID NO: 64;
l) SEQ ID NO: 66 and SEQ ID NO: 68; or
m) SEQ ID NO: 70 and SEQ ID NO: 72.
US Pat. No. 9,234,041

ANTIBODIES TO INSULIN-LIKE GROWTH FACTOR I RECEPTOR

Pfizer Inc., New York, N...

1. A method of treating cancer cells in a patient in need thereof, wherein said cancer cells express IGF-I or IGF-IR, comprising:
providing a monoclonal antibody, or an antigen-binding portion thereof, that specifically binds to human insulin-like growth
factor I receptor (IGF-IR) and comprises a heavy chain CDR1, CDR2, and CDR3 amino acid sequence of antibody 4.9.2 and a light
chain CDR1, CDR2, and CDR3 amino acid sequence of antibody 4.9.2, and wherein antibody 4.9.2 is the antibody produced by the
hybridoma deposited under ATCC Accession Number PTA-2789; and

administering a pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion thereof to the patient.
US Pat. No. 9,328,169

HUMAN ANTIBODIES THAT BIND HUMAN MADCAM

Pfizer Inc., New York, N...

1. A human monoclonal antibody that specifically binds to MAdCAM, wherein the antibody comprises the amino acid sequences
in SEQ ID NO: 34 and SEQ ID NO: 36 without the signal sequences; and wherein the antibody possesses at least one of the following
properties:
(a) has a selectivity for MAdCAM over VCAM or fibronectin of at least 100 fold;
(b) binds to human MAdCAM with a Kd of 3×10?10 M or less; and

(c) inhibits the binding of ?4?7 expressing cells to human MAdCAM.

US Pat. No. 9,238,691

NUCLEIC ACIDS ENCODING ANTIBODIES TO CCR2

Pfizer Inc., New York, N...

1. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a heavy chain and a light chain of a human
monoclonal antibody or an antigen-binding portion thereof that specifically binds to human CCR2, wherein the heavy chain of
the antibody comprises HCDR1-3 whose amino acid sequences are set forth in SEQ ID NOs:84-86, respectively; and the light chain
of the antibody comprises LCDR1-3 whose amino acid sequences are set forth in SEQ ID NOs:102-104, respectively.
US Pat. No. 9,439,902

DIOXA-BICYCLO[3.2.1]OCTANE-2,3,4-TRIOL DERIVATIVES

Pfizer Inc., New York, N...

1. A method for treating obesity in humans comprising the step of administering to a human in need of such treatment a therapeutically
effective amount of a pharmaceutical composition comprising: (i) (1S,2S,3S,4R,5S)-5-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol;
(ii) a pharmaceutically acceptable excipient, diluent, or carrier and (iii) metformin; or a pharmaceutically acceptable salt
thereof.

US Pat. No. 9,328,104

SELECTIVE ANDROGEN RECEPTOR MODULATORS

Pfizer Inc., New York, N...

1. A compound of Formula 1, 2 or 3:

wherein A is N or —CR0—, where R0 is hydrogen, C1-C6 linear or branched chain alkyl, C1-C6 linear or branched chain perfluoroalkyl, aryl, perfluoroaryl, alkylaryl, heteroaryl; or, alkylheteroaryl

X and Y are independently —CH2—, —CHRa—, or, —CRaRb—, where Ra and Rb are independently C1-C6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or, alkylheteroaryl; or, Ra and Rb together form a chain comprising —(CH2)j—, —(CHRc)j—, or —(CRcRd)j—, where Rc and Rd are independently C1-C6 linear or branched chain alkyl, C1-C6 linear or branched chain perfluoroalkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where j is 2; 3, 4 or 5

Z is —CRe, —, or, —N—, where Re is hydrogen, C1-C6 linear or branched chain alkyl, C1-C6 linear or branched chain perfluoroalkyl, aryl, alkylaryl, heteroaryl or, alkylheteroaryl;

R1 is hydrogen, C1-C6 linear or branched chain alkyl, aryl, C1-C6 linear or branched chain perfluoroalkyl, alkylaryl, heteroaryl, alkylheteroaryl, C1-C6 linear or branched chain alkoxylcarbonyl, C1-C6 linear or branched chain alkylamino-carbonylamino, C1-C6 linear or branched chain alkyloxycarbonylamino, C1-C6 linear or branched chain alkylcarbonylamino, or, C1-C6 linear or branched chain alkylaminocarbonyl;

R2 are independently hydrogen or C1-C6 linear or branched chain alkyl;

R3 and R4 are independently hydrogen, C1-C6 linear or branched chain alkyl, C1-C6 linear or branched chain perfluoroalkyl, C1-C6 linear or branched chain perfluoroalkoxy, halogen, cyano, hydroxyl, amino, carboxy, hydroxyl, aryl, heteroaryl, C1-C6 linear or branched chain alkoxylcarbonyl, C1-C6 linear or branched chain alkylamino-carbonylamino, or, C1-C6 linear or branched chain alkylaminocarbonyl;

R5 and R6 are independently hydrogen or C1-C6 linear or branched chain alkyl, C1-C6 linear or branched chain perfluoroalkyl, cyano, hydroxyl, amino, carboxy, hydroxyl, aryl, heteroaryl, or, R5 and R6 together form a chain comprising —(CH2)k—, —(CHR7)k—, or —(CR7aR7b)k—, where R7, R7a, and R7b are independently C1-C6 linear or branched chain alkyl, C1-C6 linear or branched chain perfluoroalkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where k is 2; 3, 4 or 5;

R8 is hydrogen, C1-C6 linear or branched chain alkyl, C1-C6 linear or branched chain perfluoroalkyl, aryl, aryl substituted with one, two or three fluorine atoms, perfluoroaryl, alkylaryl,
heteroaryl; or, alkylheteroaryl; or, R1 and R8 together form a chain comprising —(CH2)m—, —(CHRf)m—, or —(CRfRg)m—, where Rf and Rg are independently C1-C6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where m is 2; 3, 4 or 5;

R9 and R10 are independently hydrogen or C1-C6 linear or branched chain alkyl, C1-C6 linear or branched chain perfluoroalkyl, cyano, hydroxyl, amino, carboxy, hydroxyl, aryl, heteroaryl, or, R9 and R10 together form a chain comprising —(CH2)p—, —(CHRh)p—, or —(CRhRi)p—, where Rh and Ri are independently C1-C6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where p is 2; 3, 4 or 5;

Q is —CO—, —(CH2)q—, —(CHRs)q—, or —(CRsRt)q—, where Rs and Rt are independently C1-C6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where q is 0, 1, 2, or 3; and, where n is
0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof.

US Pat. No. 9,296,745

DIACYLGLYCEROL ACYLTRANSFERASE 2 INHIBITORS

Pfizer Inc., New York, N...

13. A pharmaceutical composition comprising a compound according to claim 1 or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer, present in a therapeutically effective
amount, in admixture with at least one pharmaceutically acceptable excipient.

US Pat. No. 9,156,845

4-(SUBSTITUTED AMINO)-7H-PYRROLO[2,3-D] PYRIMIDINES AS LRRK2 INHIBITORS

Pfizer Inc., New York, N...

1. A compound of Formula I

or a pharmaceutically acceptable salt thereof wherein
R1 and R2 taken together with the nitrogen to which they are attached are morpholin-4-yl, thiomorpholin-4-yl, 6-oxa-3-aza-bicyclo[3.1.1]heptan-3-yl,


each of which is optionally substituted with one to three R7;

R3 is phenyl or a five to ten membered heteroaryl which contains one to four heteroatoms selected from N, O and S; wherein the
phenyl and five to ten membered heteroaryl are optionally substituted with one to three R9 and wherein the phenyl is optionally fused with a C5-C6cycloalkyl or a five to six membered heterocycloalkyl which contains one to three heteroatoms selected from N, O and S and
which is optionally substituted with oxo;

R4 and R5 are each independently hydrogen or C1-C3alkyl;

R6 at each occurrence is independently selected from C1-C3alkyl, C1-C3alkoxy, hydroxy, halo, —NRaRb, —C(O)NRaRb, or a four to seven membered heterocycloalkyl which contains one to three heteroatoms selected from N, O and S;

R7 at each occurrence is independently selected from halo, hydroxy, cyano, —NRaRb, —C(O)NRaRb, C1-C6alkyl, C1-C6alkoxy, phenyl, a five to six membered heteroaryl containing one to four heteroatoms selected from N, O and S, or two R7 when attached to the same carbon and taken together can be oxo; wherein the C1-C6alkyl, phenyl and five to six membered heteroaryl are optionally substituted with one to three R8;

R8 at each occurrence is independently hydroxy, halo, cyano, C1-C3alkoxy, NRaRb, C1-C3alkyl optionally substituted with one to three halo, C3-C7cycloalkyl, phenoxy optionally substituted with cyano, or a five to six membered heteroaryloxy containing one to four heteroatoms
selected from N, O and S and which is optionally substituted with one or two halo or C1-C3alkyl;

R9 at each occurrence is independently cyano, halo, hydroxy, C1-C3alkyl-S—, —CO2H, —C(O)NH2, —S(O)2NH2, C1-C3alkyl optionally substituted with one to three halo or hydroxy, or C1-C3alkoxy optionally substituted with one to three halo or hydroxy; and

Ra and Rb at each occurrence are each independently hydrogen, C1-C6alkyl, C3-C7cycloalkyl or —C(O)C1-C6alkyl.

US Pat. No. 9,050,342

BENEFICIAL EFFECTS OF COMBINATION THERAPY ON CHOLESTEROL

Pfizer Inc., New York, N...

1. A method of treating a disease in a mammal, wherein the disease is selected from the group consisting of atherosclerosis,
myocardial infarction, hypercholesterolemia, hyperlipidemia, ischemic heart disease, congestive heart failure, acute coronary
syndrome, plaque instability, coronary artery disease, cerebrovascular disease, peripheral vascular disease and cardiac risk
management, comprising administering to a mammal in need thereof a therapeutically effective amount of a Janus Kinase inhibitor
and a HMG-CoA reductase inhibitor or a pharmaceutically acceptable salt thereof or a pharmaceutical composition of pharmaceutical
composition comprising:
a Janus Kinase inhibitor or a pharmaceutically acceptable salt thereof; and
a HMG-CoA reductase inhibitor or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable carrier.

US Pat. No. 9,303,013

CONJUGATES AND ASSOCIATED METHODS OF PRODUCING THEM FOR THE PREVENTION OR TREATMENT OF NICOTINE ADDICTION

Pfizer Inc., New York, N...

1. A method for producing a compound of formula (VII):
comprising the steps of:
(i) combining a compound of formula (IIIA) or (IIIB):
with a first base;
(ii) reacting the product of step (i) with an iodide source, a metal catalyst, and a ligand;
(iii) reacting the product of step (ii) with ethylene glycol, a second base and a metal catalyst;
(iv) producing a compound of formula (V):

(v) reacting said compound of formula (V) with tosyl chloride and an amine base;
(vi) producing and isolating a compound of formula (VI):

(vii) reacting said isolated compound of formula (VI) with an ammonia source; and
(viii) yielding the resulting compound of formula (VII).
US Pat. No. 9,180,123

N-LINK HYDROXAMIC ACID DERIVATIVES USEFUL AS ANTIBACTERIAL AGENTS

Pfizer Inc., New York, N...

1. A pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisting
of
(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2,3,4-trifluorophenyl)pyridin-1(2H)-yl]butanamide;
(2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;
(2R)-4-(4-(2-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;
(2R)-N-hydroxy-4-[4-{4-[(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;
(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}butanamide;
or a pharmaceutically acceptable salt thereof; in admixture with at least one pharmaceutically acceptable excipient.
US Pat. No. 9,409,981

ANTIBODY TO GDF8 AND USES THEREOF

Pfizer Inc., New York, N...

1. A method of treating a GDF8-associated disorder in a subject, comprising administering to a subject in need of treatment
for a GDF8-associated disorder a therapeutically effective amount of an anti-GDF8 antibody or antigen binding fragment thereof
that specifically binds to GDF8 comprising:
an antibody variable heavy (VH) region comprising the first, second and third complementarity determining regions (CDRs) from
the VH region defined by the amino acid sequence of SEQ ID NO:14 or SEQ ID NO:17; and

an antibody variable light (VL) region comprising the first, second and third CDRs from the VL region defined by the amino
acid sequence of SEQ ID NO:16 or SEQ ID NO:18,

wherein the GDF8-associated disorder is selected from the group consisting of a muscular disorder and a neuromuscular disorder,
wherein the muscular disorder or neuromuscular disorder is characterized by insufficient muscle mass or strength.

US Pat. No. 9,308,204

DIOXA-BICYCLO[3.2.1]OCTANE-2,3,4-TRIOL DERIVATIVES

Pfizer Inc., New York, N...

1. A pharmaceutical composition comprising: (i) (1S,2S,3S,4R,5S)-5-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol;
(ii) a pharmaceutically acceptable excipient, diluent, or carrier; and (iii) sitagliptin.

US Pat. No. 9,056,831

PROCESS FOR FORMING AMORPHOUS ATORVASTATIN

Pfizer Inc., New York, N...

1. The process for forming amorphous atorvastatin comprising:
(a) dissolving atorvastatin in a hydroxylic solvent containing an antioxidant selected from the group consisting of: a chelating
agent; a free-radical scavenger, and an oxygen scavenger, or mixture thereof; and

(b) lyophilizing the solution to afford said amorphous atorvastatin.
US Pat. No. 9,309,536

RECOMBINANT VIRUS-LIKE PARTICLES ENCODED BY MULTI-GENE VECTOR

PFIZER INC., New York, N...

1. A single baculoviral vector encoding a recombinant virus-like particle comprising two or more different surface proteins
comprising epitopes, wherein the surface proteins are selected from (a) different viral strains of a same virus type, (b)
different serotypes of a same virus type, or (c) different viral strains of a same virus type specific for different hosts;
and wherein the baculoviral vector comprises a polynucleotide sequence selected from SEQ ID NOs:1 to 5.
US Pat. No. 9,249,112

SOLID FORMS OF A TRANSTHYRETIN DISSOCIATION INHIBITOR

PFIZER INC., New York, N...

1. A crystalline form of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole meglumine, wherein said crystalline form has a powder
X-ray diffraction pattern comprising peaks at diffraction angles (2?) of 10.7±0.2, 11.8±0.2, and 13.3±0.2.

US Pat. No. 9,249,186

CYTOTOXIC PEPTIDES AND ANTIBODY DRUG CONJUGATES THEREOF

Pfizer Inc., New York, N...

1. A compound of formula IIIa:

or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence,

R1 is hydrogen, C1-C8 alkyl or C1-C8 haloalkyl;

R2 is hydrogen, C1-C8 alkyl or C1-C8 haloalkyl;

R3A and R3B are either of the following:

(i) R3A is C1-C8 alkyl, C1-C8 haloalkyl, C3-C8 carbocyclyl, C1-C10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; and

R3B is C1-C8 alkyl, C1-C8 haloalkyl, C3-C8 carbocyclyl, C1-C10 heterocyclyl, aryl, heteroaralkyl, halogen or aralkyl; or

(ii) R3A and R3B taken together are C2-C8 alkylene or C1-C8 heteroalkylene;

R4A and R4B are either of the following:

(i) R4A is hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C3-C8 carbocyclyl, C1-C10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and

R4B is hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C3-C8 carbocyclyl, C1-C10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or

(ii) R4A and R4B taken together are C2-C8 alkylene or C1-C8 heteroalkylene;

R5 is


optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of C1-C8 alkyl, —O—(C1-C8 alkyl), —C(O)R?, —OC(O)R?, —C(O)OR?, —C(O)NH2, —C(O)NHR?, —C(O)N(R?)2, —NHC(O)R?, —S(O)2R?, —S(O)R?, —OH, halogen, —N3, —NH2, —NH(R?), —N(R?)2, —CN, —NHC(?NH)NH2, —NHCONH2, —S(?O)2R? and —SR?, wherein each R? is independently selected from the group consisting of hydrogen, C1-C8 alkyl and unsubstituted aryl;

R11 is


Y is —C2-C20 alkylene-, —C2-C20 heteroalkylene-, C3-C8 carbocyclo-, -arylene-, —C3-C8heterocyclo-, —C1-C10alkylene-arylene-, -arylene-C1-C10alkylene-, —C1-C10alkylene-(C3-C8carbocyclo)-, —(C3-C8carbocyclo)-C1-C10alkylene-, —C1-C10alkylene-(C3-C8heterocyclo)-, or —(C3-C8 heterocyclo)-C1-C10alkylene-;

Z is

 or —NH2;

R7 is independently selected for each occurrence from the group consisting of F, Cl, I, Br, NO2, CN and CF3;

R10 is hydrogen, —C1-C10alkyl, —C3-C8carbocycle, aryl, —C1-C10heteroalkyl, —C3-C8heterocyclo, —C1-C10alkylene-aryl, -arylene-C1-C10alkyl, —C1-C10alkylene-(C3-C8carbocyclo), —(C3-C8 carbocyclo)-C1-C10alkyl, —C1-C10alkylene-(C3-C8heterocyclo), and —(C3-C8 heterocyclo)-C1-C10alkyl, where aryl on R10 comprising aryl is optionally substituted with [R7]h;

h is 1, 2, 3, 4 or 5; and
X is O or S;
R6 is hydrogen, C1-C8 alkyl or C1-C8 haloalkyl; and

h is 1, 2, 3, 4 or 5.

US Pat. No. 9,056,865

PYRIDINE-2-DERIVATIVES AS SMOOTHENED RECEPTOR MODULATORS

Pfizer Inc., New York, N...

18. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

US Pat. No. 9,290,496

PURINE DERIVATIVES

PFIZER INC., New York, N...

1. A compound of formula (IIIa):
wherein
R1 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4-6 membered heterocycloalkyl, or 4-6 membered heteroaryl, wherein the C1-C6 alkyl is optionally substituted by one, two or three substituents selected from the group consisting of halogen, hydroxy,
and C1-C3 alkoxy, further wherein the C3-C6 cycloalkyl, the 4-6 membered heterocycloalkyl, and the 4-6 membered heteroaryl are each independently optionally substituted
by one, two or three substituents selected from the group consisting of C1-C3 alkyl, hydroxy, and C1-C3 alkoxy;

R2 and R5 are each independently hydrogen, halogen, cyano, difluoromethyl, trifluoromethyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, —N(R10)(R11), C3-C5 cycloalkyl, or 4-6 membered heterocycloalkyl, wherein the C1-C6 alkyl is optionally substituted by one, two or three substituents selected from the group consisting of halogen, hydroxy,
C1-C6 alkoxy, and —N(R12)(R13),

provided that at least one of R2 or R5 is hydrogen;

R3 is hydrogen, halogen, C1-C6 alkyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C7 cycloalkyl, or 3-7 membered heterocycloalkyl, wherein the C1-C6 alkyl and the C1-C6 alkoxy are each optionally substituted by one, two or three R14 groups, and further wherein the C3-C7 cycloalkyl and the 3-7 membered heterocycloalkyl are each optionally substituted by one, two or three R15 groups;

R6 and R8 are each independently hydrogen, halogen, cyano, hydroxy, difluoromethyl, trifluoromethyl, C1-C3 alkyl, C1-C3 alkoxy, or C3-C5 cycloalkyl, wherein the C1-C3 alkyl is optionally substituted by hydroxy, difluoromethyl, trifluoromethyl, C1-C3 alkoxy, or C3-C5 cycloalkyl;

R7 is


G is —NR18—;

R10 and R11 are each independently hydrogen or C1-C6 alkyl; or R10 and R11 together with the nitrogen to which they are attached, may combine to form a 4-7 membered heterocycloalkyl ring, when R10 and R1l are each C1-C3 alkyl, wherein the 4-7 membered heterocycloalkyl ring formed is optionally substituted by one, two, three or four R15 groups;

R12 and R13 are each independently hydrogen or C1-C3 alkyl;

each R14 is independently halogen, cyano, C1-C3 alkyl, hydroxy, C1-C6 alkoxy,—N(R19)(R20), —CON(R21)(R22), or 3-7 membered heterocycloalkyl, wherein the 3-7 membered heterocycloalkyl is optionally substituted by one, two, three
or four R15 groups;

each R15 is independently halogen, C1-C3 alkyl, hydroxy, C1-C6 alkoxy, —NH2, —NHCH3, or —N(CH3)2;

R16 and R17 are each independently hydrogen or C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted by —N(R23)(R24),

provided that R16 and R17 may form C3-C5 cycloakyl ring;

R18 is hydrogen or C1-C3 alkyl;

each R19, R20, R21, R22, R23, and R24 is independently hydrogen or C1-C3 alkyl;

n is 0, 1, or 2; and
p is 0, 1, or 2; or
a pharmaceutically acceptable salt thereof.

US Pat. No. 9,139,538

QUINOLINYL GLUCAGON RECEPTOR MODULATORS

Pfizer Inc., New York, N...

1. A compound of Formula Ia?
or a pharmaceutically acceptable salt thereof, wherein
R1 is (C1-C6)alkyl which is optionally substituted with one to three fluoro, hydroxy or methoxy; (C3-C7)cycloalkyl which is optionally substituted with one to two fluoro or one to two (C1-C3)alkyl which are each optionally substituted with one to three fluoro and wherein one carbon of the (C3-C7)cycloalkyl can be replaced with an O; or (C3-C7)cycloalkyl-(C1-C6)alkyl wherein the (C3-C7)cycloalkyl group of said (C3-C7)cycloalkyl-(C1-C6)alkyl is optionally substituted with one to two (C1-C3)alkyl which are each optionally substituted with one to three fluoro;

R2 is hydrogen or (C1-C3)alkyl;

R3? is —(CH2)2CO2R, —CH2CHFCO2R, or —CH2CH(OH)CO2R;

R is (C1-C4)alkyl, benzyl, para-methoxybenzyl, or diphenylmethylene;

A1 and A2 are each independently CR4 ;

R4 at each occurrence is independently hydrogen, halo, cyano, (C1-C3)alkyl optionally substituted with one to three fluoro, (C1-C3)alkoxy optionally substituted with one to three fluoro, or (C3-C5)cycloalkyl;

B1, B2, B3 and B4 are each independently CR5; and

R5 at each occurrence is independently hydrogen, halo, cyano, (C1-C3)alkyl optionally substituted with one to three fluoro, or (C1-C3)alkoxy optionally substituted with one to three fluoro, or (C3-C5)cycloalkyl.

US Pat. No. 9,328,096

TROPOMYOSIN-RELATED KINASE INHIBITORS

Pfizer Inc., New York, N...

1. 5-(2,4-dichloro-5-(pyridin-2-yl)benzamido)-N-(2-hydroxy-2-methylpropyl)-1-phenyl-1H-pyrazole-3-carboxamide, or a pharmaceutically
acceptable salt thereof.
US Pat. No. 9,309,195

SALT FORMS OF [R-(R*,R*)]-2-(4-FLUOROPHENYL)-?, ?-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1-HEPATANOIC ACID

Pfizer Inc., New York, N...

1. An atorvastatin olamine having an x-ray powder diffraction pattern containing the following 2? peaks measured using CuK?
radiation: 8.5, 9.8, 17.4, 18.6, 20.9, 22.5, and 24.1, or a solid state 19F nuclear magnetic resonance having the following
chemical shifts measured in parts per million: ?118.7.
US Pat. No. 9,119,839

CANCER TREATMENT

Pfizer Inc., New York, N...

1. A method for treating mesothelioma, comprising administering to a patient having mesothelioma an anti-CTLA4 antibody or
an antigen-binding portion thereof as monotherapy in a multiple dose regimen, each dose having an identical dosage in the
range of 1-20 mg/kg body weight, wherein the heavy chain CDR1-3 and light chain CDR1-3 of said antibody comprise the amino
acid sequences set forth in
a) SEQ ID NOs: 1-6, respectively;
b) SEQ ID NOs: 9-14, respectively;
c) SEQ ID NOs: 17-22, respectively; or
d) SEQ ID NOs: 25-30, respectively.

US Pat. No. 9,371,298

PROCESSES FOR THE PREPARATION OF ISOTHIAZOLE DERIVATIVES

Pfizer Inc., New York, N...

1. A process for the preparation of a compound of Formula II

or a pharmaceutically acceptable salt thereof, wherein
R1 is H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, —C(O)(C1-C10 alkyl), —(CH2)t(C6-C10 aryl), —(CH2)t(4-10 membered heterocyclic), —C(O)(CH2)t(C6-C10 aryl), or —C(O)(CH2)t(4-10 membered heterocyclic), wherein t is an integer from 0 to 5; said alkyl group optionally includes 1 or 2 hetero moieties
selected from O, S and —N(R6)— with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other; said aryl and
heterocyclic R1 groups are optionally fused to a C6-C10 aryl group, a C5-C8 saturated cyclic group, or a 4-10 membered heterocyclic group;

1 or 2 carbon atoms in the foregoing heterocyclic moieties are optionally substituted by an oxo (?O) moiety; and the foregoing
R1 groups, except H, are optionally substituted by 1 to 3 R4 groups;

R2 is selected from the list of substituents provided in the definition of R1, —SO2(CH2)t(C6-C10 aryl), —SO2(CH2)t(4-10 membered heterocyclic), and —OR5, t is an integer ranging from 0 to 5, and the foregoing R2 groups are optionally substituted by 1 to 3 R4 groups;

or R1 and R2 may be taken together with the nitrogen to which each is attached to form a 4-10 membered saturated monocyclic or polycyclic
ring or a 5-10 membered heteroaryl ring, wherein said saturated and heteroaryl rings optionally include 1 or 2 heteroatoms
selected from O, S and —N(R6)— in addition to the nitrogen to which R1 and R2 are attached, said —N(R6)— is optionally ?N— or —N? where R1 and R2 are taken together as said heteroaryl group, said saturated ring optionally may be partially unsaturated by including 1 or
2 carbon-carbon double bonds, and said saturated and heteroaryl rings, including the R6 group of said —N(R6)—, are optionally substituted by 1 to 3 R4 groups;

R3 is H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, —(CH2)t(C6-C10 aryl), or —(CH2)t(4-10 membered heterocyclic), wherein t is an integer from 0 to 5; said alkyl group optionally includes 1 or 2 hetero moieties
selected from O, S and —N(R6)— with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other; said aryl and
heterocyclic R3 groups are optionally fused to a C6-C10 aryl group, a C5-C8 saturated cyclic group, or a 4-10 membered heterocyclic group;

1 or 2 carbon atoms in the foregoing heterocyclic moieties are optionally substituted by an oxo (?O) moiety; the —(CH2)t— moieties of the foregoing R3 groups optionally include a carbon-carbon double or triple bond where t is an integer from 2 to 5, and the foregoing R3 groups are optionally substituted by 1 to 5 R4 groups;

each R4 is independently selected from halo, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, nitro, trifluoromethyl, trifluoromethoxy, azido, —OR5, —NR6C(O)OR5, —NR6SO2R5, —SO2NR5R6, —NR6C(O)R5, —C(O)NR5R6, —NR5R6, —S(O)jR7 wherein j is an integer ranging from 0 to 2, —NR5(CR6R7)tOR6, —(CH2)t(C6-C10 aryl), —SO2(CH2)t(C6-C10 aryl), —S(CH2)t(C6-C10 aryl), —O(CH2)t(C6-C10 aryl), —(CH2)t(4-10 membered heterocyclic), and —(CR6R7)mOR6, wherein m is an integer from 1 to 5 and t is an integer from 0 to 5; said alkyl group optionally contains 1 or 2 hetero
moieties selected from O, S and —N(R6)— with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other; said aryl and
heterocyclic R4 groups are optionally fused to a C6-C10 aryl group, a C5-C8 saturated cyclic group, or a 4-10 membered heterocyclic group; 1 or 2 carbon atoms in the foregoing heterocyclic moieties
are optionally substituted by an oxo (?O) moiety; and the alkyl, aryl and heterocyclic moieties of the foregoing R4 groups are optionally substituted by 1 to 3 substituents independently selected from nitro, trifluoromethyl, trifluoromethoxy,
azido, —NR6SO2R5, —SO2NR5R6, —NR6C(O)R5, —C(O)NR5R6, —NR5R6, —(CR6R7)mOR6 wherein m is an integer from 1 to 5, —OR5 and the substituents listed in the definition of R5;

each R5 is independently selected from H, C1-C10 alkyl, —(CH2)t(C6-C10 aryl), and —(CH2)t(4-10 membered heterocyclic), wherein t is an integer from 0 to 5;

said alkyl group optionally includes 1 or 2 hetero moieties selected from O, S and —N(R6)— with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other; said aryl and
heterocyclic R5 groups are optionally fused to a C6-C10 aryl group, a C5-C8 saturated cyclic group, or a 4-10 membered heterocyclic group; and the foregoing R5 substituents, except H, are optionally substituted by 1 to 3 substituents independently selected from nitro, trifluoromethyl,
trifluoromethoxy, azido, —NR6C(O)R7, —C(O)NR6R7, —NR6R7, hydroxy, C1-C6 alkyl, and C1-C6 alkoxy;

each R6 and R7 is independently H or C1-C6 alkyl;
R8 is H, C1-C10 alkyl, —C(O)(C1-C10 alkyl), —C(O)(C6-C10 aryl), —C(O)(4-10 membered heterocyclic), —(CH2)t(C6-C10 aryl), —(CH2)t(4-10 membered heterocyclic), —C(O)O(C1-C10 alkyl); —C(O)O(C6-C10 aryl), —C(O)O(4-10 membered heterocyclic) wherein t is an integer from 0 to 5;
said aryl and heterocyclic R8 groups are optionally fused to a C6-C10 aryl group; and the foregoing aryl and heterocyclic R8 groups are optionally substituted with 1-2 substituents independently selected from halogen, trifluoromethyl, C1-C6 alkoxy, C1-C6 alkyl, and nitro groups; comprising (1) reacting a compound of Formula IV


wherein R3, R4, R5, R6, R7 and R8 are as defined above for Formula II with a source of carbonyl, with or without an added base, and then adding a compound of
Formula III

HNR1R2  III
wherein R1 and R2 are as defined above for Formula II in a solvent to give a compound of the Formula II or (2) reacting a compound of Formula
III with a source of carbonyl, with or without an added base, and then adding a compound of Formula IV in a solvent to give
a compound of the Formula II, wherein the compound of Formula II is selected from the group consisting of:
3-(4-Bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido}-isothiazole-4-carboxylic acid methyl ester;
5-{3-[3-(4-Methyl-piperazin-1-yl)-propyl]-ureido}-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl
ester;

3-(4-Chloro-2,6-difluoro-benzyloxy)-5-(3-{4-[ethyl-(2-hydroxy-ethyl)-amino]-butyl}-ureido)-isothiazole-4-carboxylic acid methyl
ester;

3-(2-Fluoro-4-methyl-benzyloxy)-5-{3-[3-(4-methyl-piperazin-1-yl)-propyl]-ureido}-isothiazole-4-carboxylic acid methyl ester;
3-(2,5-Difluoro-4-methyl-benzyloxy)-5-(3-4-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-butyl}-ureido)-isothiazole-4-carboxylic acid
methyl ester;

3-(2,5-Difluoro-4-methyl-benzyloxy)-5-[3-(6-dimethylamino-hexyl)-ureido]-isothiazole-4-carboxylic acid methyl ester;
3-(2-Fluoro-4-methyl-benzyloxy)-5-[3-(5-isopropylamino-pentyl)-ureido]-isothiazole-4-carboxylic acid methyl ester;
hydrochloride salt of 3-(4-Bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido}-isothiazole-4-carboxylic acid
methyl ester;

3-(4-Chloro-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid methyl ester;
3-(4-Chloro-2,6-difluoro-benzyloxy)-5-{3-[3-(4-methyl-piperazin-1-yl)-propyl]-ureido}-isothiazole-4-carboxylic acid methyl
ester;

3-(4-Chloro-2,6-difluoro-benzyloxy)-5-{3-[-(1-methyl-pyrrolidin-2-yl)-ethyl]-ureido}-isothiazole-4-carboxylic acid methyl
ester;

3-(2,6-Difluoro-4-methyl-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid methyl ester;
3-(2,6-Difluoro-4-methyl-benzyloxy)-5-[3-{4-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-butyl}-ureido)-isothiazole-4-carboxylic acid
methyl ester;

3-(4-Chloro-2,6-difluoro-benzyloxy)-5-[3-(3-hydroxy-5-pyrrolidin-1-yl)-pentyl)-ureido}-isothiazole-4-carboxylic acid methyl
ester;

3-(2,5-Difluoro-4-methyl-benzyloxy)-5-{3-[4-(3,4-dihydroxy-pyrrolidin-1-yl]-butyl]-ureido}-isothiazole-4-carboxylic acid methyl
ester;

3-(4-Chloro-2,6-difluoro-benzyloxy)-5-{3-[4-(3,4-dihydroxy-pyrrolidin-1-yl)-butyl]-ureido}-isothiazole-4-carboxylic acid methyl
ester;

3-(2,5-Difluoro-4-methyl-benzyloxy)-5-{3-[4-(2-hydroxymethyl-pyrrolidin-1-yl)-butyl]-ureido}-isothiazole-4-carboxylic acid
methyl ester;

3-(4-Chloro-2,6-difluoro-benzyloxy)-5-{3-[4-(2-hydroxymethyl-pyrrolidin-1-yl)-butyl]-ureido}-isothiazole-4-carboxylic acid
methyl ester;

3-(2,5-Difluoro-4-methyl-benzyloxy)-5-{3-[4-(3-hydroxy-pyrrolidin-1-yl)-butyl]-ureido}-isothiazole-4-carboxylic acid methyl
ester;

3-(4-Bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl]-ureido}-isothiazole-4-carboxylic acid methyl ester;
3-(2,6-Difluoro-4-methyl-benzyloxy)-5-[3-(4-hydroxy-5-piperidin-1-yl-pentyl)-ureido]-isothiazole-4-carboxylic acid methyl
ester;

3-(2,5-Difluoro-4-methyl-benzyloxy)-5-{3-[4-(3-hydroxy-5-piperidin-1-yl-pentyl)-ureido]-isothiazole-4-carboxylic acid methyl
ester;

3-(4-Chloro-2,6-difluoro-benzyloxy)-5-{3-[4-(2-hydroxymethyl-piperidin-1-yl)-butyl]-ureido}-isothiazole-4-carboxylic acid
methyl ester;

3-(2,5-Difluoro-4-methyl-benzyloxy)-5-(3-{4-[ethyl-(2-hydroxy-ethyl)-amino]-butyl}-ureido)-isothiazole-4-carboxylic acid methyl
ester;

3-(4-Chloro-2,6-difluoro-benzyloxy)-5-[3-(5-hydroxy-6-piperidin-1-yl)-hexyl)-ureido}-isothiazole-4-carboxylic acid methyl
ester;

3-(4-Bromo-2,3,6-trifluoro-benzyloxy)-5-{3-[3-(4-methyl-piperazin-1-yl)-propyl]-ureido}-isothiazole-4-carboxylic acid methyl
ester;

3-(2,6-Difluoro-4-methyl-benzyloxy)-5-{3-[3-(4-methyl-piperazin-1-yl-propyl]-ureido}-isothiazole-4-carboxylic acid methyl
ester;

3-(2,6-Difluoro-4-methyl-benzyloxy)-5-[3-(3-hydroxy-5-pyrrolidin-1-yl-pentyl)-ureido]-isothiazole-4-carboxylic acid methyl
ester;

5-[3-(4-Pyrrolidin-1-yl-butyl)-ureido]-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl ester;
5-[3-(3-Hydroxy-5-pyrrolidin-1-yl-pentyl)-ureido]-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl
ester;

3-(4-Chloro-2,6-difluoro-benzyloxy)-5-{3-[3-(5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl)-propyl]-ureido}-isothiazole-4-carboxylic
acid methyl ester;

3-(4-Chloro-2,3,6-trifluoro-benzyloxy)-5-{3-[3-(5-methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-propyl]-ureido}-isothiazole-4-carboxylic
acid methyl ester;

3-(4-Chloro-2,3,6-trifluoro-benzyloxy)-5-{3-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-ureido}-isothiazole-4-carboxylic acid methyl
ester;

3-(4-Chloro-2,3,6-trifluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid methyl ester;
3-(4-Chloro-2,3,6-trifluoro-benzyloxy)-5-{3-[4-(2-hydroxymethyl-pyrrolidin-1-yl)-butyl]-ureido}-isothiazole-4-carboxylic acid
methyl ester;

5-{3-[2-(1-Methyl-pyrrolidin-2-yl)-ethyl]-ureido}-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl
ester;

5-[3-(4-Dimethylamino-butyl)-ureido]-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl ester;
5-[3-(3-Dimethylamino-propyl)-ureido]-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl ester;
5-[3-(3-Hydroxy-5-isopropropylamino-pentyl)-ureido]-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl
ester;

5-[3-(3-Isopropylamino-propyl)-ureido]-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl ester;
5-{3-[4-(4-Methyl-piperazin-1-yl)-butyl]-ureido}-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl
ester;

5-(3-{4-[4-(2-Hydroxy-ethyl)-piperazin-1-yl]-butyl}-ureido)-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic
acid methyl ester;

5-[3-(3-Pyrrolidin-1-yl-propyl)-ureido]-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl ester;
5-[3-(4-Hydroxy-5-piperidin-1-yl-pentyl)-ureido]-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl
ester;

3-(4Chloro-2,6-difluoro-benzyloxy)-5-[3-(4-imidazol-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid methyl ester;
5-(3-{4-[Ethyl-(2-hydroxy-ethyl)-amino]-butyl}-ureido)-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid
methyl ester;

3-(4-Chloro-(2,3,6-trifluoro-benzyloxy)-5-{3-[4-(2-hydroxmethyl-piperidin-1-yl)-butyl]-ureido}-isothiazole-4-carboxylic acid
methyl ester;

3-(4-Chloro-2,3,6-trifluoro-benzyloxy)-5-[3-(3-hydroxy-5-pyrrolidin-1-yl-pentyl)-ureido]-isothiazole-4-carboxylic acid methyl
ester;

3-(4-Bromo-2,6-difluoro-benzyloxy)-5-{3-[3-(4-methyl-piperazin-1-yl)-propyl]-ureido}-isothiazole-4-carboxylic acid methyl
ester;

3-(2,6-Difluoro-4-methyl-benzyloxy)-5-{3-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-ureido}-isothiazole-4-carboxylic acid methyl
ester;

3-(2,6-Difluoro-4-methyl-benzyloxy)-5-[3-(4-dimethylamino-butyl)-ureido}-isothiazole-4-carboxylic acid methyl ester;
3-(2,6-Difluoro-4-methyl-benzyloxy)-5-[3-(3-dimethylamino-propyl)-ureido]-isothiazole-4-carboxylic acid methyl ester;
3-(4-Bromo-2,3,6-trifluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid methyl ester;
3-(4-Chloro-2,3,6-trifluoro-benzyloxy)-5-[3-(4-imidazol-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid methyl ester;
3-(4-Chloro-2,3,6-difluoro-benzyloxy)-5-(3-{3-[ethyl-(2-hydroxy-ethyl)-amino]-propyl}-ureido)-isothiazole-4-carboxylic acid
methyl ester;

3-(4-Chloro-2,3,6-trifluoro-benzyloxy)-5-(3-{3-[ethyl-(2-hydroxy-ethyl)-amino]-propyl}-ureido)-isothiazole-4-carboxylic acid
methyl ester;

5-[3-(3-Methylamino-propyl)-ureido]-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl ester;
5-[3-(3-Amino-propyl)-3-methyl-ureido]-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl ester;
5-[3-(4-Diethylamino-butyl)-ureido]-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl ester;
3-(2,6-Difluoro-4-methyl-benzyloxy)-5-[3-(3-pyrrolidin-1-yl-propyl)-ureido]-isothiazole-4-carboxylic acid methyl ester;
3-(3-Chloro-2,6-difluoro-4-methyl-benzyloxy)-5-[3-(4-dimethylamino-butyl)-ureido]-isothiazole-4-carboxylic acid methyl ester;
and

5-(3-{4-[Bis-(2-hydroxy-ethyl)-amino]-butyl}-ureido)-3-(2,6-difluoro-4-methyl-benzyloxy)-isothiazole-4-carboxylic acid methyl
ester;

and pharmaceutically acceptable salts thereof.

US Pat. No. 9,315,520

2-AMINO-6-METHYL-4,4A,5,6-TETRAHYDROPYRANO[3,4-D][1,3]THIAZIN-8A(8H)-YL-1,3-THIAZOL-4-YL AMIDES

Pfizer Inc., New York, N...

1. A compound of Formula I

wherein
R1 is selected from the group consisting of:

phenyl optionally substituted with one to three R2;

C3-9cycloalkyl optionally substituted with one to three R2; and

a 5- to 10-membered heteroaryl, having one to four heteroatoms independently selected from N, O or S, wherein at least one
of the heteroatoms is N and wherein said N is optionally substituted with R3; and wherein said 5- to 10-membered heteroaryl is optionally substituted on carbon with one to three R2;

R2 at each occurrence is independently selected from the group consisting of halogen, hydroxy, cyano, C1-6alkyl, C1-6alkoxy, C3-6alkenyl, C3-6alkenyloxy, C3-6alkynyl, C3-6alkynyloxy, C1-6alkoxy-C1-6alkyl, C3-6cycloalkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkoxy, C3-6cycloalkyl-C1-6alkoxy, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl; wherein said C1-6alkyl, C1-6alkoxy, C3-6alkenyl, C3-6alkenyloxy, C3-6alkynyl, C3-6alkynyloxy, C1-6alkoxy-C1-6alkyl, C3-6cycloalkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C3-6cycloalkyl-C1-6alkoxy, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl are each optionally substituted with one to three substituents independently selected from fluoro, chloro, hydroxy,
cyano, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy and trifluoromethoxy;
or two R2 groups taken together can be a C3-5alkylene; and

R3 is selected from the group consisting of hydrogen, C1-6alkyl, C3-6alkenyl, C3-6alkynyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl; wherein said C1-6alkyl, C3-6alkenyl, C3-6alkynyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl are each optionally substituted with one to three substituents independently selected from fluoro, chloro, hydroxy,
cyano, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy and trifluoromethoxy;
or R3 and R2 taken together can be a C3-5alkylene;

or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer.
US Pat. No. 9,248,189

ANTI-GLUCAGON RECEPTOR ANTIBODIES AND PHARMACEUTICAL COMPOSITIONS THEREOF

PFIZER INC., New York, N...

1. An isolated antagonist antibody that specifically binds to glucagon receptor and comprises:
a heavy chain variable region (VH) comprising a VH complementarity determining region one (CDR1), VH CDR2, and VH CDR3 of
the VH having the amino acid sequence shown in SEQ ID NO: 11; and

a light chain variable region (VL) comprising a VL CDR1, VL CDR2, and VL CDR3 of the VL having the amino acid sequence shown
in SEQ ID NO: 10.

US Pat. No. 9,205,078

N-METHYL-2-[3-((E)-2-PYRIDIN-2-YL-VINYL)-1H-INDAZOL-6-YLSULFANYL]-BENZAMIDE FOR THE TREATMENT OF CHRONIC MYELOGENOUS LEUKEMIA

PFIZER INC., New York, N...

1. A method of treating chronic myelogenous leukemia in a subject comprising administering to the subject a compound that
inhibits the T315I mutation in BCR-ABL tyrosine kinase, wherein the compound is N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide,
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,428,577

PLATELET-DERIVED GROWTH FACTOR B SPECIFIC ANTIBODIES AND COMPOSITIONS AND USES THEREOF

Pfizer Inc., New York, N...

1. An isolated antibody, or antigen-binding fragment thereof, that specifically binds PDGF-B and comprises:
a VH comprising the CDR-H1 amino acid sequence of SEQ ID NO:7, the CDR-H2 amino acid sequence of SEQ ID NO:8, and the CDR-H3 amino
acid sequence of SEQ ID NO: 9; and

a VL comprising the CDR-L1 amino acid sequence of SEQ ID NO:10, the CDR-L2 amino acid sequence of SEQ ID NO:11, and the CDR-L3
amino acid sequence of SEQ ID NO:12.

US Pat. No. 9,296,761

TRIAZINE DERIVATIVES

Pfizer Inc., New York, N...

1. A method for the treatment of Huntington's disease comprising administering to a patient in need thereof an effective amount
of a compound, of the formula:
or a pharmaceutically acceptable salt thereof, in which:
A, along with X and the carbon atom to which it is attached, forms a (C6-C10)aryl or a 5- to 10-membered heteroaryl moiety, in which said aryl or heteroaryl moiety is optionally substituted with up
to 4 substituents, each independently selected from the group consisting of C3-C6 cycloalkyl, oxo, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, hydroxy, cyano, halo, —NR5R6, —C(O)—NR5R6, —NH—C(O)R5, —C(O)—OR5, —(C1-C6)alkyl-(C3-C6)cycloalkyl, a 4- to 6-membered heterocyclic moiety, phenyl, and benzyl; X is represented by N or C; R1 is represented by C1-C6 alkyl, (C6-C10)aryl or a 5- to 6-membered heterocyclic moiety, in which said alkyl, aryl or heterocyclic moiety may be optionally substituted
with up to 4 substituents, each independently selected from the group consisting of halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, hydroxy, cyano, —NR5R6, —C(O)—NR5R6, —NH—C(O)R5, and —C(O)—OR5; R2 and R3 are each independently represented by hydrogen, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 alkoxy; R4, if present, is optionally represented by up to 2 substituents, each independently selected from the group consisting of
fluoro, hydroxy, optionally substituted C1-C6alkyl, or optionally substituted C1-C6 alkoxy, and; R5 and R6 are each optionally and independently represented by hydrogen or C1-C6 alkyl.

US Pat. No. 9,181,252

N1/N2-LACTAM ACETYL-COA CARBOXYLASE INHIBITORS

Pfizer Inc., New York, N...

1. A compound of structure

or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,073,871

GLUCAGON RECEPTOR MODULATORS

Pfizer Inc., New York, N...

1. A compound of structure

US Pat. No. 9,045,498

HEXAHYDROPYRANO[3,4-D][1,3]THIAZIN-2-AMINE COMPOUNDS

Pfizer Inc., New York, N...

1. A compound of Formula I,
wherein
R1 is hydrogen or methyl, wherein said methyl is optionally substituted with one to three substituents independently selected
from halogen or methoxy;

R2 is C1-6 alkyl, —(C(R5)2)m—(C3-6 cycloalkyl), —C(R5)2)m—(C6-10 aryl), —(C(R5)2)m— (5- to 10-membered heteroaryl) or —(C(R5)2)t—OR6; wherein said alkyl, cycloalkyl, aryl or heteroaryl moieties are optionally substituted with one to three substituents independently
selected from halogen, C1-6 alkyl, —CH2F, —CHF2, —CF3, —CN or —OR7;

R3 is —C(R5)2)m—(CN);

R4 is independently selected from halogen, C1-6 alkyl or C1-6 alkoxy; wherein said alkyl or alkoxy is optionally substituted with one to three fluoro;

R5 at each occurrence is independently selected from hydrogen or C1-3 alkyl, wherein said alkyl is optionally substituted with one to three halogen;

R6 is hydrogen, C1-6 alkyl or —C(R5)2)n—(C6-10 aryl), wherein said alkyl and aryl are optionally substituted with one to three substituents independently selected from halogen,
C1-3 alkyl, —CH2F, —CHF2, —CF3, —CN or —OH;

R7 for each occurrence is hydrogen or C1-6 alkyl, wherein said alkyl is optionally substituted with one to three substituents independently selected from halogen or
C1-6 alkoxy;

m at each occurrence is independently 0, 1 or 2;
n at each occurrence is independently is 1 or 2;
t is 1 or 2; and
x is 0, 1, 2 or 3;
or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer.
US Pat. No. 9,308,166

ENHANCED STABILITY OF NOVEL LIQUID COMPOSITIONS

Pfizer Inc., New York, N...

1. A liquid oral pharmaceutical composition comprising:
i.) from about 0.1% to about 20% w/v polyvinylpyrrolidone;
ii.) from about 5% to about 70% w/v polyethylene glycol;
iii.) from about 1% to about 30% w/v propylene glycol;
iv.) from about 1% to 10% w/v guaifenesin; and
v.) from about 0.01% to about 1.0% w/v phenylephrinewherein the composition is visually free of guaifenesin precipitation for at least 62 days at 4° C.

US Pat. No. 9,192,612

HETEROARYL-SUBSTITUTED HEXAHYDROPYRANO[3,4-D][1,3]THIAZIN-2-AMINE COMPOUNDS

Pfizer Inc., New York, N...

1. A method of treating Alzheimer's disease in a patient, the method comprising administering a therapeutically effective
amount of a-compound of Formula I
wherein
R1 is hydrogen or methyl, wherein said methyl is optionally substituted with one to three fluoro;

R2 is a 5- to 10-membered heteroaryl, having one to four heteroatoms independently selected from N, O or S, wherein at least
one of the heteroatoms is N and wherein said N is optionally substituted with R4; and wherein said 5- to 10-membered heteroaryl is optionally substituted on carbon with one to three R3;

R3 at each occurrence is independently selected from the group consisting of halogen, hydroxy, cyano, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C3-6cycloalkoxy, C3-6cycloalkoxy-(CR5aR5b)m—, C3-6cycloalkyl-(CR5aR5b)n—O—, —(CR5aR5b)m—C3-6cycloalkyl or —(CR5aR5b)m-(4- to 6-membered heterocycloalkyl);
wherein said C1-6alkyl, C1-6alkoxy or C1-6alkoxy-C1-6alkyl are each optionally substituted with one to three fluoro and wherein said C3-6cycloalkyl, C3-6cycloalkoxy and (4- to 6-membered heterocycloalkyl) moieties are optionally substituted with one to three substituents independently
selected from the group consisting of fluoro, methyl, fluoromethyl, difluoromethyl or trifluoromethyl;
R4 is hydrogen, C1-6alkyl, —(CR5aR5b)m—C3-6cycloalkyl or —(CR5aR5b)m-(4- to 6-membered

heterocycloalkyl); wherein said C1-6alkyl, C3-6cycloalkyl and -(4- to 6-membered heterocycloalkyl) moieties are each optionally substituted with one to three substituents
independently selected from fluoro, methyl, trifluoromethyl, methoxy or trifluoromethoxy;

R5a and R5b are independently hydrogen, methyl, fluoromethyl, difluoromethyl, trifluoromethyl or methoxy;

m at each occurrence is independently 0, 1 or 2; and
n is 1, 2 or 3;or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer;to a patient in need of treatment thereof.

US Pat. No. 9,399,626

2-THIOPYRIMIDINONES

Pfizer Inc., New York, N...

1. A compound having Formula I

or a pharmaceutically acceptable salt thereof
wherein
R1 is phenyl and said R1 is mono-, di-, or tri-substituted independently with hydroxyethoxy, methyl, methoxy, fluoro or chloro; and

R2 is diaminomethyleneamino(C2-C4)alkyl, carbamoyl(C1-C4)alkyl, hydroxy(C2-C4)alkyl, amino(C2-C4)alkylcarbamoyl(C1-C4)alkyl, (C1-C4)alkylcarbonylamino(C2-C4)alkyl, amino(C1-C4) alkylcarbonylamino(C2-C4)alkyl, amino(C3-C4)hydroxyalkyl or amino(C2-C4)alkyl with the proviso that 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide and N—(2-aminoethyl)-2[6-(2,4-dimethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin
-1(2H)-yl]acetamide or a pharmaceutically acceptable salt of said proviso's compounds are not included.

US Pat. No. 9,139,587

N1-PYRAZOLOSPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS

Pfizer Inc., New York, N...

1. A compound of structure
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,079,877

PROCESS FOR PREPARING CHIRAL COMPOUNDS

Pfizer Inc., New York, N...

1. 2-[2-(4,6-Dihydroxy-tetrahydro-pyran-2-yl)ethyl]-isoindole-1,3-dione.
US Pat. No. 9,428,546

TANDEM PURIFICATION OF PROTEINS

Pfizer Inc., New York, N...

1. A method of recovering a purified protein product from a load fluid, the method comprising:
a) providing a first column comprising a first resin, wherein the first resin comprises protein A;
b) providing a second column comprising a second resin, wherein the second resin comprises an anion exchange resin, wherein
the first column is arranged in tandem with the second column;

c) exposing the load fluid comprising a protein product to the first column under conditions in which the product binds to
the first resin;

d) recovering fluid comprising the product from the first resin to produce a first eluate;
e) titrating the first eluate with a titrant continuously as it passes to the second resin, wherein the titrant comprises
a pH buffer and at least 150 mM of a salt, and wherein the titrant is added at a target volumetric ratio to the first eluate
such that there is a change in partition coefficient of less than 20% when the actual volumetric ratio of the first eluate
to the titrant varies up to about 40% from the target volumetric ratio;

f) exposing the titrated eluate to the second column under conditions in which the product binds to the second resin; and
g) recovering fluid comprising the product from the second resin to produce a second eluate, thereby recovering the purified
protein product from the load fluid.

US Pat. No. 9,352,050

PROCESSES FOR PREPARING PEPTIDE CONJUGATES AND LINKERS

PFIZER INC., New York, N...

1. A process for preparing a compound according to formula 5a
comprising
(i) reacting 9a and 11 together in the presence of 1-propanephosphonic acid anhydride (T3P) to create compound 13a

(ii) catalytic hydrogenation with Pd/C of compound 13a in a THF:H2O solution of at least about 50% THF to produce a compound of formula 4a


(iii) combining a solution of 14a in THF with a compound according to formula 15 in a reaction substantially free of base
to produce compound 6a


(iv) reacting a compound according to the formula 6a with a compound according to formula 19a in THF in the presence of DCC
to produce compound 20a


(v) combining 20a with a ?-amino containing peptide 2 dissolved in an aprotic polar 15th solvent to produce compound 3a


(vi) dissolving compound 3a in DMSO;
(vii) adding histidine buffer at pH between about 5.5 to about 7.5 to the solution of DMSO and 3a of step (vi);
(viii) Adding an antibody comprising a variable light region comprising SEQ ID NO:5 and a variable heavy region comprising
SEQ ID NO:6 to the solution of step (vii), so as to have a peptide:antibody molar ratio of between about 1.8:1 to about 3:1;

(ix) Agitating the mixture formed in step (viii) at a medium speed so as to avoid foaming the reaction mixture for at least
about 1 hr at between about pH 5.5 and about pH7.5 and at a temperature of between about 5° C. and 35° C.; and

(x) Filtration of the solution from (ix) to extract the resultant peptide-linker antibody conjugate 5awherein q=1, 2, 3, 4, or 5, X=F or Cl, and m=3, 4, or 5.

US Pat. No. 9,260,455

ALKYL-SUBSTITUTED HEXAHYDROPYRANO[3,4-D][1,3]THIAZIN-2-AMINE COMPOUNDS

Pfizer Inc., New York, N...

1. A compound of Formula I,

wherein
R1 is hydrogen or methyl, wherein said methyl is optionally substituted with one to three fluoro;

R2 is C1-6alkyl or —(C(R3aR3b))m—O—C1-6alkyl; wherein said C1-6alkyl or —(C(R3aR3b))m—O—C1-6alkyl are optionally substituted with one to three substituents independently selected from the group consisting of halogen,
C1-3alkyl, —CH2F, —CHF2, —CF3, —CN or —OH;

R3a and R3b are independently hydrogen, fluoro, or C1-6alkyl; wherein said C1-6alkyl is optionally substituted with one to three fluoro; and

m is 1 or 2;
or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer.
US Pat. No. 9,107,923

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

Pfizer Inc., New York, N...

1. A compound selected from the group consisting of:
6-{4-[(3-chloro-5-fluoropyridin-2-yl)oxy]-2-methylphenyl}-1,5-dimethylpyrimidine-2,4(1H,3H)-dione;
1,5-dimethyl-6-(2-methyl-4-{[3-(trifluoromethyl)pyridin-2-yl]oxy}phenyl)pyrimidine-2,4(1H,3H)-dione; and
6-{4-[(3-chloropyridin-2-yl)oxy]-2-methylphenyl}-1,5-dimethylpyrimidine-2,4(1H,3H)-dione,or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,045,487

SALTS AND POLYMORPHS OF 8-FLUORO-2-{4-[(METHYLAMINO)METHYL]PHENYL}-1,3,4,5-TETRAHYDRO-6H-AZEPINO[5,4,3-CD]INDOL-6-ONE

PFIZER INC., New York, N...

1. A camsylate salt of 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one.

US Pat. No. 9,045,499

HETEROARYL-SUBSTITUTED HEXAHYDROPYRANO[3,4-D][1,3]THIAZIN-2-AMINE COMPOUNDS

Pfizer Inc., New York, N...

1. A compound of Formula I

wherein
R1 is hydrogen or methyl, wherein said methyl is optionally substituted with one to three fluoro;

R2 is a 6-membered heteroaryl selected from the group consisting of pyridinyl, pyridonyl, pyrimidinyl and pyrazinyl; each optionally
substituted on carbon with one to two R3; and wherein said pyridonyl is substituted on N with R4;

R3 at each occurrence is independently selected from the group consisting of halogen, cyano, C1-6alkyl, and C1-6alkoxy; wherein said alkyl is optionally substituted with one to three fluoro; and

R4 is hydrogen, methyl or trifluoroethyl;

or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer.

US Pat. No. 9,278,953

ANTAGONISTS OF PROSTAGLANDIN EP3 RECEPTOR

Pfizer Inc., New York, N...

1. A compound of Formula I:

wherein
R1 is H, C1-6alkyl, or C3-6cycloalkyl;

m is 1 or 2;
Each R2 is independently halogen, C1-6alkyl, or C3-6cycloalkyl;

n is 0 or 1;
X1, X2, and X3 are independently ?N—, —NRXn—, or ?CRXc—, provided that at least 1 but no more than 2 of X1, X2, and X3 are independently ?N— or —NRXn—;

RXn is H, C1-6alkyl, or C3-6cycloalkyl; and

Each RXc is independently H, halogen, C1-6alkyl, or C3-6cycloalkyl;

or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,468,678

METHOD OF PRODUCING 4-1BB BINDING MOLECULES AND ASSOCIATED NUCLEIC ACIDS

Pfizer Inc., New York, N...

1. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide that comprises one or more amino
acid sequences selected from SEQ ID NO: 43, 44, 45 or 46.

US Pat. No. 9,403,846

CARBOCYCLIC- AND HETEROCYCLIC-SUBSTITUTED HEXAHYDROPYRANO[3,4-D][1,3]THIAZIN-2-AMINE COMPOUNDS

Pfizer Inc., New York, N...

1. A compound of formula (I)
or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer, wherein:
R1 is selected from hydrogen, —CH3, —CH2F, —CHF2, —CF3, or —CH2OCH3;

R2 is —(C(R3a)(R3b))m—(C3-C6)cycloalkyl or —(C(R3a)(R3b))m-(4- to 10-membered) heterocycloalkyl having one to three heteroatoms independently selected from N, O or S, wherein said
N is optionally substituted with R4; and wherein each available carbon position of said (C3-C6)cycloalkyl moiety or said (4- to 10-membered)heterocycloalkyl moiety is optionally substituted with one to two R6;

R3a and R3b are each independently hydrogen, fluoro, or (C1-C6)alkyl; wherein said (C1-C6)alkyl is optionally substituted with one to three fluoro;

R4 is selected from (C1-C6)alkyl, (C1-C6)alkylcarbonyl, (C3-C6)cycloalkylcarbonyl or (C1-C6)alkylcarbonyl(C1-C6)alkyl; wherein said (C1-C6)alkyl moiety, said (C1-C6)alkylcarbonyl moiety and said (C1-C6)alkylcarbonyl(C1-C6)alkyl moiety are optionally substituted with one to three fluoro;

R5 at each occurrence is independently halogen, (C1-C3)alkyl, and (C1-C3)alkoxy, wherein said (C1-C3)alkyl moiety and said (C1-C3)alkoxy are optionally substituted with one to three fluoro;

R6 at each occurrence is independently halogen, —OH, —CN, (C1-C6)alkyl, and (C1-C6)alkoxy, wherein said (C1-C6)alkyl or (C1-C6)alkoxy is optionally substituted with one to three fluoro;

m is 0, 1, or 2; and
b is 0, 1, 2, 3, 4, or 5.

US Pat. No. 9,169,264

SPLICEOSTATIN ANALOGS AND METHODS FOR THEIR PREPARATION

Pfizer Inc., New York, N...

1. A compound of formula (I):

wherein:
a dashed line represents an optional bond;
each X1 is independently selected from the group consisting of: —O—, —S— and —NR—;

each X2 is independently selected from the group consisting of: —O—, —S— and —NR—;

R1 is selected from the group consisting of: —R, —OR, —OCOR13, —OCONR14R15, —OCON(R14)NR(R15), ?O (double bond to oxygen) and —NR14R15;

R2 and R3 are independently selected from the group consisting of: hydrogen and C1-6alkyl;

R4 and R5 are independently selected from the group consisting of: hydrogen, —OR, —NR14R15 and oxo;

R6 and R7 are independently selected from the group consisting of: hydrogen, halogen, hydroxyl and C1-6alkyl optionally substituted with 1-3 substituents independently selected from hydroxyl and halogen,

R6 and R7, together with the carbon atom to which they are bound, form a C2-5alkylidene optionally substituted with 1-3 substituents independently selected from R,

R6 and R7 together are oxo, or

R6 and R7, together with the carbon atom to which they are bound, form a 3- to 5-membered heterocycloalkyl moiety comprising 1 or 2
heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, wherein said heterocycloalkyl
moiety may be optionally substituted with one to three substituents independently selected from R;

R8 is hydrogen, C1-6alkyl or —OR;

R9 is independently selected from —(C(R)2)m—C(O)OR, —(C(R)2)m—C(O)NR14R15, —(C(R)2)m—NR14R15, —(C(R)2)m—N(R)COR13, —(C(R)2)m—C(O)—SR, —(C(R)2)m—C(O)NR14N(R)R15, —(C(R)2)m—NR—C(O)—NR14R15 and —(C(R)2)m—NR14N(R)R15;

R13 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8carbocyclyl, C3-8heterocyclyl, C1-6alkyl-C6-14aryl, C1-6alkyl-C5-14heteroaryl, wherein R13 is optionally substituted with —NRR or —SO2NRR;

each R14 and R15 is independently selected from the group consisting of: hydrogen, hydroxyl, —NRR, —NRNR2, —C3-10carbocyclyl, —C1-6alkylene-C3-10carbocyclyl, —C3-10heterocyclyl, —C1-6alkylene-C3-10heterocyclyl, -(CH2CH2O)1-6CH2CH2C(O)OR, -(CH2CH2O)1-6CH2CH2NRR, —C1-6alkyl, C6-14aryl, —C1-6alkylene-C6-14aryl and —C5-14heteroaryl;

or R14 and R15, together with the atom or atoms to which they are joined, form a C3-10heterocyclyl ring,

wherein R14, R15, or both, or a ring formed with R14 and R15, are optionally substituted with —C(R)2)m—R18 where each R18 is independently selected from (i) —NRR, (ii) —C(NRR)(C(O)OR), (iii) —S—R, (iv) aryl or heteroaryl optionally substituted
with one or more of halogen, —CF3, —(C(R)2)m—NRR or —(C(R)2)m—SO2NRR, (v) —SO2R, (vi) —S—S—C1-6alkyl-C(O)OR, (vii) —SO2NRR, (viii) —C(O)NRR, (ix) —C(O)OR, (x) —C4-6 cycloalkyl optionally substituted with —NRR, —SO2NRR or —NR—C(O)(CH2)0-6NRR, (xi) —R, (xii) —OR, (xiii) —N(R)NRR, (xiv) —C(O)N(R)NRR, —(C(R)2)m—O—NRR and —S—S—C1-6alkyl-NRR;

each R is independently selected from the group consisting of: hydrogen and —C1-6alky; and

each m is independently 0, 1, 2 or 3;
or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,260,439

DIHYDROPYRROLOPYRIMIDINE DERIVATIVES

PFIZER INC., New York, N...

1. A compound of formula (II)
or a pharmaceutically acceptable salt thereof,wherein
R1 is hydrogen, methyl, —CH2OH, or —CH2F;

y is 0 or 1;
R2 is hydrogen, cyano, C1-C3 alkyl, or —CF3;

R3 is hydrogen or C1-C3 alkyl;

ring A is C3-C8 cycloalkyl or 4-8 membered heterocycloalkyl;

Q is —C(R9)(R10)—, —N(R11)— or —O—;

x is 0, 1, 2, 3, or 4;
each R4a is independently selected from the group consisting of fluorine, cyano, oxo, methyl, —CH2F, —CHF2, —CF3, —CH2OH, hydroxy, and methoxy;

R9 is hydrogen,

fluorine,
cyano,
hydroxy,
C1-C3 alkoxy,

—S(O)R32,

—O—S(O)2R33,

—[N(R26)]h—C(O)R34,

—[N(R27)]i—C(O)[N(R35)(R36)],

—[N(R28)]j—C(O)OR37,

—[N(R29)]k—S(O)2R38,

—[N(R30)]l—S(O)2[N(R39)(R40)], or

—[N(R31)]o—P(O)(CH3)2;

R10 is hydrogen, fluorine, or C1-C3 alkyl;

R11 is hydrogen,

—(CH2)p—C(O)R41,

—(CH2)q—C(O)[N(R42)(R43)],

—(CH2)r—C(O)OR44,

—(CH2)s—S(O)2R45,

—(CH2)t—S(O)2[N(R46)(R47)],

—(CH2)u—R48, or

—P(O)(CH3)2,

R26, R27, R28, R29, R30 and R31 are each independently hydrogen or methyl;

h, i, j, k, l, o, p, q, r, s, t, and u are each independently 0 or 1;
R32 is C1-C4 alkyl, wherein the C1-C4 alkyl is optionally substituted by one substituent selected from the group consisting of fluorine, cyano, hydroxy, C1-C4 alkoxy, —NH2, —NHCH3, and —N(CH3)2;

R33 is C1-C4 alkyl, —NH2, —NHCH3, —N(CH3)2, or C3-C5 cycloalkyl, wherein the C1-C4 alkyl is optionally substituted by one substituent selected from the group consisting of fluorine, cyano, hydroxy, C1-C4 alkoxy, —NH2, —NHCH3, and —N(CH3)2;

R34 and R41 are each independently hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, 4-6 membered heterocycloalkyl, or 5 membered heteroaryl, wherein the C1-C4 alkyl, the C3-C6 cycloalkyl, and the 4-6 membered heterocycloalkyl are each independently optionally substituted by one, two, or three substituents
selected from the group consisting of fluorine, cyano, oxo, C1-C4 alkyl, —CH2F, —CHF2, —CF3, hydroxy, C1-C4 alkoxy, —C(O)NH2, —C(O)OH, —C(O)OCH3, —NH2, —NHCH3, —N(CH3)2, —[N(R49)]-C(O)R50, C3-C4 cycloalkyl, and 4-5 membered heterocycloalkyl, further wherein the 5 membered heteroaryl is optionally substituted by one
substituent selected from the group consisting of fluorine, cyano, hydroxy, methoxy, —NH2, and —NHCH3;

R35 and R42 are each independently hydrogen, C1-C4 alkyl, C3-C4 cycloalkyl, or 4-5 membered heterocycloalkyl;

R36 and R43 are each independently hydrogen or C1-C4 alkyl; or

R35 and R36 together with the nitrogen to which they are attached and R42 and R43 together with the nitrogen to which they are attached, each independently form a 4-5 membered heterocycloalkyl ring, wherein
the 4-5 membered heterocycloalkyl ring formed is optionally substituted by one, two, or three substituents selected from the
group consisting of fluorine, cyano, oxo, C1-C4 alkyl, hydroxy, and methoxy;

R37 and R44 are each independently C1-C4 alkyl, C3-C4 cycloalkyl, or 4-5 membered heterocycloalkyl, wherein the C1-C4 alkyl is optionally substituted by one, two, or three substituents selected from the group consisting of fluorine, cyano,
hydroxy, methoxy, —C(O)NH2, —C(O)NHCH3, —C(O)N(CH3)2, —NH—S(O)2NH2, —NH—S(O)2NHCH3, and —NH—S(O)2N(CH3)2, further wherein the C3-C4 cycloalkyl and the 4-5 membered heterocycloalkyl are each optionally substituted by one or two substituents selected from
the group consisting of fluorine, cyano, methyl, hydroxy, methoxy, and —C(O)CH3;

R38 and R45 are each independently C1-C4 alkyl, —CF3, C1-C4 alkoxy, —(CH2)v—(C3-C4 cycloalkyl), 4-5 membered heterocycloalkyl, or 5-6 membered heteroaryl, wherein the C1-C4 alkyl is optionally substituted by one substituent selected from the group consisting of fluorine, cyano, hydroxy, and methoxy,
further wherein the 4-5 membered heterocycloalkyl and the 5-6 membered heteroaryl are each independently optionally substituted
by one or two substituents selected from the group consisting of fluorine, cyano, C1-C4 alkyl, hydroxy, methoxy, —C(O)(C1-C4 alkyl), and —C(O)[O—(C1-C4 alkyl)];

v is 0 or 1;
R39 and R46 are each independently hydrogen, C1-C4 alkyl, C3-C4 cycloalkyl, or 4-5 membered heterocycloalkyl;

R40 and R47 are each independently hydrogen or C1-C4 alkyl; or

R39 and R40 together with the nitrogen to which they are attached and R46 and R47 together with the nitrogen to which they are attached, each independently form a 4-5 membered heterocycloalkyl ring, wherein
the 4-5 membered heterocycloalkyl ring formed is optionally substituted by one or two substituents selected from the group
consisting of fluorine, cyano, C1-C4 alkyl, hydroxy, and methoxy;

R48 is C1-C4 alkyl, C3-C4 cycloalkyl, or 4-6 membered heterocycloalkyl, wherein the C1-C4 alkyl is optionally substituted by one, two, or three substituents selected from the group consisting of fluorine, cyano,
hydroxy, methoxy, —C(O)NH2, —C(O)NHCH3, —C(O)N(CH3)2, —NH2, —NHCH3, and —N(CH3)2, further wherein the C3-C4 cycloalkyl and the 4-6 membered heterocycloalkyl are each optionally substituted by one, two, three, or four substituents
selected from the group consisting of fluorine, cyano, methyl, hydroxy, methoxy, oxo, —CF3, and —C(O)CH3;

R49 is hydrogen or methyl; and

R50 is C1-C4 alkyl, —CF3, C1-C4 alkoxy, —NH2, —NHCH3, —N(CH3)2, C3-C5 cycloalkyl, or 4-6 membered heterocycloalkyl.

US Pat. No. 9,233,981

SUBSTITUTED PHENYL HEXAHYDROPYRANO[3,4-D][1,3]THIAZIN-2-AMINE COMPOUNDS

Pfizer Inc., New York, N...

1. A compound of Formula I

wherein
R1 is hydrogen or methyl, wherein said methyl is optionally substituted with one to three fluoro;

R2 is phenyl substituted with one to five R3;

R3 at each occurrence is independently selected from the group consisting of halogen, hydroxy, cyano, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C3-6cycloalkoxy, C3-6cycloalkyl-(CR4aR4b)m—, C3-6cycloalkoxy-(CR4aR4b)m—, C3-6Cycloalkyl-(CR4aR4b)m—O— or (4- to 6-membered heterocycloalkyl)-(CR4aR4b)m—; wherein said C1-6alkyl, C1-6alkoxy or C1-6alkoxy-C1-6alkyl are each optionally substituted with one to three fluoro and wherein said C3-6cycloalkyl, C3-6cycloalkoxy and (4- to 6-membered heterocycloalkyl) moieties are optionally substituted with one to three substituents independently
selected from the group consisting of fluoro, methyl, fluoromethyl, difluoromethyl or trifluoromethyl; or two R3, when attached to adjacent carbons on the phenyl and taken together, can be —(CH2)n—O—, —O—(CH2)o—O— or —(CH2)p—;

R4a and R4b are independently hydrogen, methyl, fluoromethyl, difluoromethyl, trifluoromethyl or methoxy;

m at each occurrence is independently 0, 1 or 2;
n is 2 or 3;
is 1 or 2; and
p is 3 or 4;
or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer.
US Pat. No. 9,963,508

HUMAN MONOCLONAL ANTIBODIES TO CTLA-4

AMGEN FREMONT INC., Thou...

1. An isolated cell line that produces a monoclonal anti-CLTA-4 antibody or an antigen-binding portion thereof, wherein the antibody or antigen-binding portion comprises a CDR1 sequence, a CDR2 sequence and a CDR3 sequence of a heavy chain and a light chain having the sequences of:(a) SEQ ID NOs: 86 and 112, respectively;
(b) SEQ ID NOs: 73 and 95, respectively;
(c) SEQ ID NOs: 75 and 89, respectively;
(d) SEQ ID NOs: 76 and 92, respectively;
(e) SEQ ID NOs: 77 and 93, respectively;
(f) SEQ ID NOs: 78 and 90, respectively;
(g) SEQ ID NOs: 79 and 91, respectively;
(h) SEQ ID NOs: 81 and 97, respectively;
(i) SEQ ID NOs: 82 and 98, respectively;
(j) SEQ ID NOs: 83 and 114, respectively; and
(k) SEQ ID NOs: 84 and 116, respectively.
US Pat. No. 9,481,666

SUBSTITUTED DIHYDROISOQUINOLINONE COMPOUNDS

PFIZER INC., New York, N...

1. A compound that is 5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-[(R)-methoxy(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one.
US Pat. No. 9,468,672

PROSTATE-ASSOCIATED ANTIGENS AND VACCINE-BASED IMMUNOTHERAPY REGIMENS

Pfizer Inc., New York, N...

1. A method of treating prostate cancer in a human, comprising administering to the human an effective amount of a composition
1 comprising a multi-antigen construct, wherein the multi-antigen construct comprises:
(a) at least one nucleotide sequence encoding an immunogenic PSA polypeptide;
(b) at least one nucleotide sequence encoding an immunogenic PSCA polypeptide; and
(c) at least one nucleotide sequence encoding an immunogenic PSMA polypeptide, wherein the immunogenic PSA polypeptide comprises
amino acids 4-240 of SEQ ID NO:17, wherein the immunogenic PSCA polypeptide comprises the amino acid sequence of SEQ ID NO:21,
and wherein the immunogenic PSMA polypeptide has at least 90% identity with amino acids 15-750 of the human PSMA of SEQ ID
NO:1 and comprises the amino acids of at least 10 conserved T cell epitopes of the human PSMA at corresponding positions.

US Pat. No. 9,133,215

MACROCYCLIC DERIVATIVES FOR THE TREATMENT OF DISEASES

Pfizer Inc., New York, N...

1. A compound of formula (VI)
wherein:
A is a ring selected from C6-C12 aryl and 5-6 membered heteroaryl;

R1 is selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl, wherein each hydrogen on said C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, —OH,
—NH2, —S(O)tR9, —S(O)2NR9R10 , —S(O)2OR9, —NO2, —CN, —OR9, —C(O)R9, —OC(O)R9, —NR9C(O)R10, —C(O)OR9, —C(?NR9)NR9R10, —NR9 C(O)NR9R10, —NR or —C(O)NR9R10;

each R2 is independently selected from the group consisting of halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, —S(O)tR7, —S(O)2NR7R8, —S(O)2OR7, —NO2, —(CR5R6)qNR7R8, —N(CR5R6)(CR5R6)qNH7R8, —OR7, —O(CR5R6)(CR5R6)qOR7, —O(CR5R6)(CR5R6)qR7, —CN, —C(O)R7, —OC(O)R7, —O(CR5R6)qR7, —NR7C(O)R8, —(CR5R6)qC(O)OR7, —(CR5R6)qNR7R8, —C(?NR7)NR7R8, —NR7C(O)NR7R8, —NR7S(O)2R8 and —(CR5R6)qC(O)NR7R8; wherein each hydrogen on said C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, —OH,
—NH2, —S(O)tR9, —S(O)2NR9R10, —S(O)2OR9, —NO2, —OR9, —CN, —C(O)R9,—OC(O)R9, —NR9C(O)R10, —C(O)OR9, —C(?NR9)NR9R10, —NR9C(O)NR9R10—NR9S(O)2R10or —C(O)NR9R10;

R3 and R4 are each independently selected from hydrogen, C1-C6 alkyl and C3-C6 cycloalkyl, wherein each hydrogen on C1-C6 alkyl and C3-C6 cycloalkyl may be independently optionally substituted by halogen, —OH, —NH2, —S(O)tR9, —S(O)2NR9R10, —S(O)2OR9, —NO2, —CN, —OR9, —C(O)R9,—OC(O)R9, —NR9C(O)R10, —C(O)OR9, —C(?NR9)NR9R10, —NR9C(O)NR9R10, —NR9S(O)2R10or —C(O)NR9R10;

each R5 and R6 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, —OH, —NH2, —S(O)tR9, —S(O)2NR9R10, —S(O)2OR9, —NO2, —CN, —OR9, —C(O)R9,—OC(O)R9, —NR9C(O)R1° , —C(O)OR9, —C(?NR9)NR9R10, —NR9C(O)NR9R10, —NR9S(O)2R10and —C(O)NR9R10; wherein each hydrogen on said C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, —OH,
—NH2, —S(O)tR9, —S(O)2NR9R10, —S(O)2OR9, —NO2, —CN, —OR9, —C(O)R9, —OC(O)R9,—NR9C(O)R10, —C(O)OR9, —C(?NR9)NR9R1° , —NR —NR or —C(O)NR9R10;

each R7 and R8 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl, wherein each hydrogen on said C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, —OH,
—NH2, —S(O)tR9, —S(O)2NR9R10, —S(O)2OR9, —NO2, —OR9, —CN, —C(O)R9, —OC(O)R9, —NR9C(O)R10, —C(O)OR9, —C(?NR9)NR9R10, —NR9S(O)2R10or —C(O)NR9R10;

each R9 and R10is independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl;

p is 0, 1, 2, 3 or 4;
each q is independently 0, 1, 2 or 3; and
each t is independently 0, 1 or 2;
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,452,134

APIXABAN SOLUTION FORMULATIONS

Bristol-Myers Squibb Comp...

1. A liquid formulation comprising apixaban and a vehicle, wherein:
water content of the vehicle is about 20% to about 30% w/w of the vehicle; non-ionic surfactant content of the vehicle is
about 11% to about 14% w/w of the vehicle;

ionic surfactant content of the vehicle is about 0.2% to about 1% w/w of the vehicle;
hydrophilic polymer content of the vehicle is about 1% to about 6% w/w of the vehicle;
polyhydric alcohol content of the vehicle is about 31% to about 37% w/w of the vehicle;
polyethylene glycol content of the vehicle is about 4% to about 6% w/w of the vehicle; and
carbohydrate content of the vehicle is about 18% to about 22% w/w of the vehicle;
wherein a solubility of apixaban in the vehicle is at least 0.50 mg/mL.

US Pat. No. 9,340,493

HYDROXAMIC ACID DERIVATIVES USEFUL AS ANTIBACTERIAL AGENTS

Pfizer Inc., New York, N...

1. A compound of formula (I):
or a pharmaceutically acceptable salt thereof, thereof, wherein:
G is a group of formula (II)

A is phenyl of formula (III)

or a 6-membered heteroaryl of formula (IV)

wherein said phenyl or said 6-membered heteroaryl of said A is optionally substituted by one to four R4 groups;

B is —(C6-C10)aryl or —(C1-C9)heteroaryl;

L1 is either absent or a linker moiety selected from the group consisting of —C(O)— and —C(O)N(R7)—;

L2 is absent or a —(C1-C6)alkylene- linker moiety; wherein said —(C1-C6)alkylene- linker moiety of said L2 may optionally be substituted by one to three groups independently selected from the group consisting of -halo, —OH and —N(R7)2;

L3 is absent or a linker moiety selected from the group consisting of —C(O)—, —N(R7)—, —C(O)N(R7)—, —N(R7)C(O)—, —S(O)j—, and —S(O)jN(R7)—;

L4 is absent or a —(C1-C6)alkylene- linker moiety; wherein said —(C1-C6)alkylene- linker moiety of said L4 may optionally be substituted by one to three groups independently selected from the group consisting of -halo, —OH and —N(R7)2;

R1 is selected from the group consisting of —OH, -halo, —(C1-C6)alkyl, -perfluorinated(C1-C6)alkyl, —O(C1-C6)alkyl, —(C3-C6)alkenyl, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; wherein each of said —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C2-C6)alkenyl, —(C3-C10)cycloalkyl, —(C2-C9heterocycloalkyl, —(C6-C10)aryl and —(C1-C9)heteroaryl of said R1 is optionally substituted with one to three R5 groups;

R2 is selected from the group consisting of —(C1-C6)alkyl, -perfluorinated(C1-C6)alkyl, —O(C1-C6)alkyl, —(C2-C6)alkenyl, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; wherein each of said —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C2-C6)alkenyl, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10)aryl and —(C2-C9)heteroaryl of said R2 is optionally substituted with one to three groups selected from the group consisting of —OH, -halo, —N(R7)2, —N(R7)C(O)R9, —C(O)N(R7)2, —S(O)jR8, —N(R7)S(O)jR8, —S(O)jN(R7)2, -perfluorinated(C1-C6)alkyl, —O(C -C6)alkyl, and —O(perfluorinated(C1-C6)alkyl); or

R1 and R2 together with the carbon atom to which they are attached may form a 3- to 7-membered carbocyclic ring when both L1 and L2 are absent or a 4- to 7-membered heterocyclic ring when both L1 and L2 are absent; wherein each of said 3- to 7-membered carbocyclic ring or a 4- to 7-membered heterocyclic ring formed by the joinder
of R1 and R2 is optionally substituted by one to three R5 groups;

each R3 is independently selected from the group consisting of —H, —OH, -halo, —S(O)jR8, —S(O)jN(R7)2, —(C1-C6)alkyl, —O(C1-C6)alkyl, -perfluorinated(C1-C6)alkyl, O(perfluorinated(C1-C6)alkyl), —(C2-C6)alkenyl, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; wherein each of said —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10)aryl and —(C1-C9) heteroaryl of said R3 is optionally independently substituted with one to three R6 groups;

each R4 is independently selected from the group consisting of —OH, -halo, —CN, —C(O)R9, —N(R7)2, —N(R7)C(O)R9, —C(O)N(R7)2, —N(R7)S(O)jR8, —S(O)jN(R7)2, —OP(O)(OH)2, —(C1-C6)alkyl, —(C1-C6)alkyl, perfluorinated(C1-C6)alkyl, —O(C1-C6)alkyl, —O(perfluorinated(C1-C6)alkyl), —(C2-C6)alkenyl, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10)aryl and —(C1-C9)heteroaryl; wherein each of said —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C2-C6)alkenyl, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10)aryl and —(C1-C9)heteroaryl of said R4 is optionally independently substituted with one to three groups selected from the group consisting of —OH, -halo, —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl;

each R5 is independently selected from the group consisting of —OH, -halo, —CN, —N(R7)2, —N(R7)C(O)R9, —C(O)N(R7)2, —S(O)jR8, —N(R7)S(O)jR8, —S(O)jN(R7)2, —OP(O)(OH)2, —(C1-C6)alkyl, perfluorinated(C1-C6)alkyl, —O(C1-C6)alkyl, O(perfluorinated(C1-C6)alkyl), —(C2-C6)alkenyl, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10)aryl and —(C1-C9)heteroaryl; wherein each of said —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C2-C6)alkenyl, —(C3 -C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10)aryl and —(C1-C9)heteroaryl of said R5 is optionally independently substituted with one to three groups selected from the group consisting of —OH, -halo, —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl ;

each R6 is independently selected from the group consisting of —OH, -halo, —CN, —N(R7)2, —N(R7)C(O)R9, —C(O)N(R7)2, —S(O)R8, —N(R7)S(O)jR8, —S(O)jN(R7)2, —CF3, —(C1-C6)alkyl, —O(C1-C6)alkyl, -perfluorinated(C1-C6)alkyl, —O(perfluorinated(C1-C6)alkyl), —(C2-C6)alkenyl, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10)aryl, —(C1-C9)heteroaryl, —(C1-C6)alkylene-OH, —(C1-C6)alkylene-halo, —(C1-C6)alkylene-N(R7)2, —(C1-C6)alkylene-N(R7)C(O)R8, —(C1-C6)alkylene-S(O)jR8, —(C1-C6)alkylene-perfluorinated (C1-C6)alkyl, —(C1 -C6)alkylene-O(C1-C6)alkyl, —(C1-C6)alkylene-O(perfluorinated(C1-C6)alkyl), —(C1-C6)alkylene-(C3-C10)cycloalkyl, —(C1-C6)alkylene(C2-C9)heterocycloalkyl, —(C1-C6)alkylene-(C1-C6)alkyl, —(C1-C6)alkylene-(C6-C10)aryl, —(C1-C6)alkylene-(C1-C9)heteroaryl; wherein each of said —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C2- C6)alkenyl, —(C3-C10 )cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10)aryl and —(C1-C9)heteroaryl of said R6 is optionally independently substituted with one to three groups independently selected from the group consisting of —OH,
-halo, —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10) aryl and —(C1-C9)heteroaryl;

each R7, R8, and R9 is independently selected from the group consisting of —H, —(C1-C6)alkyl, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl;

j is 0, 1 or 2; and
m is 0, 1 or 2.

US Pat. No. 9,200,000

IMIDAZO[5,1-F][1,2,4]TRIAZINES FOR THE TREATMENT OF NEUROLOGICAL DISORDERS

Pfizer Inc., New York, N...

1. A compound of the Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
“-A-R5” is:


R1 is hydrogen, (C1-C6)alkyl, (C3-C15)cycloalkyl, —(C1-C6)alkyl-OH, —(C1-C6)alkyl-CN, —SF5, —CF3, —CHF2, or —CH2F;

R2 is —(C1-C6)alkyl-R9, —NHR3, —N(R3)2, —O—(C1-C6)alkyl-R9, —OR8, (C3-C15)cycloalkyl, (C6-C10)aryl, (3- to 14-membered)heterocyclic, and (5- to 14-membered)heteroaryl; wherein said (C3-C15)cycloalkyl and (3- to 14-membered)heterocyclic may optionally contain one double or triple bond and one to two oxo (O?) groups;
and wherein said —(C1-C6)alkyl-R9, —NHR3, —N(R3)2, —O—(C1-C6)alkyl-R9, —OR8,(C3-C15)cycloalkyl, (C6-C10)aryl, (3- to 14-membered)heterocyclic, or (5- to 14-membered)heteroaryl moieties may be optionally substituted with one to
three substituents independently selected from the group consisting of (C1-C6)alkyl, (C1-C6)alkoxy, halo, and —CF3;

Each R3 is independently selected from the group consisting of —(C1-C6)alkyl-R9, —(C2-C6)alkenyl-R9, —(C2-C6)alkynyl-R9, and —(C3-C15)cycloalkyl-R9, or when R2 is —N(R3)2 both of said R3 may be taken together with the nitrogen atom to which they are attached to form a 4- to 6-membered heterocyclic ring optionally
containing one or two oxo groups (O?) and optionally substituted with one to three substituents independently selected from
the group consisting of hydrogen, fluoro, —CN, —CF3, —CHF2, —CH2F, —OH, —O—(C1-C6)alkyl, NH2, —NH—(C1-C6)alkyl, —N[(C1-C6)alkylk]2, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C?O)—R8,—(C?O)—OR8, —(C?O)—N(R8)2, —O—(C?O)—R8, —OR8, —O—(C?O)—OR8, —SR8, —S(O)R8, —S(O)2R8, —S(O)2N(R8)2, —NH—(C?O)—R8, —NH—(C?O)—OR8, —O—(C?O)—N(R8)2, —NH—(C?O)—N(R8)2, —N[(C1-C6)alkyl](C?O)—R8, —N[(C1-C6)alkyl](C?O)—OR8, —N[(C1-C6)alkyl](C?O)—N(R8)2, (C3-C15) cycloalkyl, —(C6-C10)aryl, (3- to 14-membered) heterocyclic and (5- to 14-membered)heteroaryl; wherein said (C3-C15)cycloalkyl and (3- to 14-membered) heterocyclic moieties may optionally contain one double or triple bond and one to two
oxo (O?) groups;

Each R4 is independently selected from the group consisting of hydrogen, halo, (C1-C6) alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —CF3, —CHF2, —CH2F, and (C3-C15)cycloalkyl;

Each R4a is independently selected from the group consisting of hydrogen, (C1-C6)alkyl, (C3-C4)alkenyl, (C3-C4)alkynyl, —CF3, —CHF2, —CH2F, and (C3-C15)cycloalkyl;

R5 is:


where n is 0, 1, 2, 3, or 4;
Each R6 is independently selected from the group consisting of hydrogen, halo, (C1-C6)alkyl, —CF3, —CHF2, —CH2F, —CF2—(C1-C6)alkyl, —SF5, —CN, —(C1-C6)alkyl-CN, —NO2, —(C?O)—R8, —(C?O)—OR8, —O—(C?O)—N(R8)2, —SR8, —S(O)R8, —S(O)2R8, NH2, —NH—(C1-C6)alkyl, —N[(C1-C6)alkyl]2, —NH—(C?O)—R8,—NH—(C?O)—OR8, —N[(C1-C6)alkyl](C?O)—R8, —N[(C1-C6)alkyl](C?O)—OR8, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C15)cycloalkyl, (3- to 14-membered)heterocyclic, (C6-C10)aryl, and (5- to 14-membered)heteroaryl; wherein said (C3-C15)cycloalkyl and (3- to 14-membered)heterocyclic moieties may optionally contain one double or triple bond and one to two oxo
(O?) groups;

Each R7 is independently selected from the group consisting of hydrogen, halo, (C1-C6)alkyl, (C2-C4)alkenyl, (C2-C6)alkynyl, —CN, —CF3, —CHF2, —CH2F, —O—(C1-C6)alkyl and (C3-C15)cycloalkyl;

Each R8 wherever it occurs is independently selected from the group consisting of hydrogen, (C1-C6)alkyl, (C3-C15)cycloalkyl, —CF3, and —CHF2; and

Each R9 is independently selected from the group consisting of hydrogen, halo, —CF3, —CHF2, —CH2F, —CF2—(C1-C6)alkyl, —CN, —(C1-C6)alkyl-CN, —NO2, —(C?O)—R8, —(C?O)—OR8, —OR8, —O—(C?O)—N(R8)2, —SR8, —S(O)R8, —S(O)2R8, NH2, —NH—(C1-C6)alkyl, —N[(C1-C6)alkyl]2, —NH—(C?O)—R8, —NH—(C?O)—OR8, —N[(C1-C6)alkyl](C?O)—R8, —N[(C1-C6)alkyl](C?O)—OR8, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C15)cycloalkyl, (3- to 14-membered)heterocyclic, (C6-C10)aryl, and (5- to 14-membered)heteroaryl, wherein said (C3-C15)cycloalkyl and (3- to 14-membered)heterocyclic moieties may optionally contain one double or triple bond and one to two oxo
(O?) groups; and wherein each of said (C3-C15)cycloalkyl, (3- to 14-membered)heterocyclic, (C6-C10)aryl, and (5- to 14-membered)heteroaryl moieties may be optionally substituted with one to three substituents independently
selected from (C1-C6)-alkyl, (C1-C6)alkoxy, halo, and —CF3.

US Pat. No. 9,175,093

PCSK9 ANTAGONISTS

RINAT NEUROSCIENCE CORP.,...

1. A pharmaceutical composition comprising a therapeutically effective amount of an isolated antibody comprising a heavy chain
variable region (VH) complementary determining region one (CDR1) having the amino acid sequence shown in SEQ ID NO:8, 59,
or 60, a VH CDR2 having the amino acid sequence shown in SEQ ID NO:61 or 9, a VH CDR3 having the amino acid sequence shown
in SEQ ID NO:10, a light chain variable region (VL) CDR1 having the amino acid sequence shown in SEQ ID NO:11, a VL CDR2 having
the amino acid sequence shown in SEQ ID NO:12, and a VL CDR3 having the amino acid sequence shown in SEQ ID NO:13.

US Pat. No. 9,120,788

AZABENZIMIDAZOLE COMPOUNDS

Pfizer Inc., New York, N...

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:
R1 is represented by a substituent selected from the group consisting of (C3-C10)cycloalkyl, a (4- to 10-membered)heterocycloalkyl, (C6-C10)aryl, and a (5- to 10-membered) heteroaryl; wherein said (C3-C10)cycloalkyl, (C6-C10)aryl and (5- to 10-membered)heteroaryl are substituted with (R2)b; and said (4- to 10-membered)heterocycloalkyl is optionally substituted at one to five carbon atoms with a substituent independently
selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy, and cyano, and optionally substituted at each available nitrogen with (C1-C6)alkyl;

R2 is represented by a substituent independently selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio; —C(O)NR4R5, hydroxy, and cyano;

R3, if present, at each occurrence is represented by a substituent independently selected from the group consisting of halogen,
(C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy, and cyano;

R4 and R5 are each represented by a substituent independently selected from the group consisting of hydrogen, (C1-C6)alkyl, and (C3-C6)cycloalkyl;

one of R6 and R7 is represented by a substituent selected from the group consisting of hydrogen, (C1-C6)alkyl, —(CH2)m—(C3-C10)cycloalkyl, —(CH2)m-(4- to 10-membered)-heterocycloalkyl, —(CH2)m—(C6-C10)aryl, and —(CH2)m-(5- to 10-membered)heteroaryl and the other is represented by a substituent selected from the group consisting of (C1-C6)alkyl, —(CH2)m—(C3-C10)cycloalkyl, —(CH2)m-(4- to 10-membered)-heterocycloalkyl, —(CH2)m—(C6-C10)aryl, and —(CH2)m-(5- to 10-membered)heteroaryl; wherein:

i) said R6 and R7 (C1-C6)alkyl substituent is optionally substituted with one to five substituents independently selected from the group consisting
of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, and cyano;

ii) said R6 and R7 (C3-C10)cycloalkyl substituent is optionally substituted with one to five substituents independently selected from the group consisting
of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy and cyano;

iii) said R6 and R7 (C6-C10)aryl substituent is optionally substituted with one to five substituents independently selected from the group consisting
of halogen, (C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy and cyano;

iv) said R6 and R7 (5- to 10-membered)heteroaryl substituent is optionally substituted with one to five substituents independently selected from
the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy, and cyano; and

v) said R6 and R7 (4- to 10-membered)heterocycloalkyl substituent is optionally substituted at one to five carbon atoms with a substituent independently
selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy, and cyano, and optionally substituted at each available nitrogen with (C1-C6)alkyl; or R6 and R7 taken together with the nitrogen to which they are attached form a (4- to 10-membered)heterocycloalkyl, wherein said (4- to
10-membered) heterocycloalkyl is optionally substituted at one to five carbon atoms with a substituent independently selected
from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy, and cyano;

a is represented by an integer selected from 0, 1, 2 or 3;
b is represented by an integer selected from 0, 1, 2, 3, 4 or 5; and
m is represented by an integer selected from 0, 1, 2 or 3.
US Pat. No. 9,340,553

SUBSTITUTED-6,8-DIOXABICYCLO[3.2.1]OCTANE-2,3-DIOL COMPOUNDS AS TARGETING AGENTS OF ASGPR

Pfizer Inc., New York, N...

1. A compound selected from the group consisting of:
benzyl (4-((2-((1-(1-((1S,2R,3R,4R,5S)-4-acetamido-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]octan-1-yl)-2,5,8,11-tetraoxatridecan-13-yl)-1H-1,2,3-triazol-4-yl)methoxy)ethyl)amino)-4-oxobutyl)carbamate,
benzyl (4-((1,3-bis((1-(1-((1S,2R,3R,4R,5S)-4-acetamido-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]octan-1-yl)-2,5,8,11-tetraoxatridecan-13-yl)-1H-1,2,3-triazol-4-yl)methoxy)propan-2-yl)amino)-4-oxobutyl)carbamate,
benzyl (4-((1,3-bis((1-(1-((1S,2R,3R,4R,5S)-4-acetamido-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]octan-1-yl)-2,5,8,11-tetraoxatridecan-13-yl)-1H-1,2,3-triazol-4-yl)methoxy)-2-(((1-(1-((1S,2R,3R,4R,5S)-4-acetamido-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]octan-1-yl)-2,5,8,11-tetraoxatridecan-13-yl)-1H-1,2,3-triazol-4-yl)methoxy)methyl)propan-2-yl)amino)-4-oxobutyl)carbamate,
N-(2-((1-(1-((1S,2R,3R,4R,5S)-4-acetamido-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]octan-1-yl)-2,5,8,11-tetraoxatridecan-13-yl)-1H-1,2,3-triazol-4-yl)methoxy)ethyl)-4-aminobutanamide,
4-amino-N-{1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]propan-2-yl}butanamide,
4-amino-N-(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)butanamide,
4-amino-N-[1,31-bis(1-{[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]methyl}-1H-1,2,3-triazol-4-yl)-2,6,10,14,18,22,26,30-octaoxahentriacontan-16-yl]butanamide,
4-amino-N-{1,31-bis(1-{[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]methyl}-1H-1,2,3-triazol-4-yl)-16-[15-(1-{[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]methyl}-1H-1,2,3-triazol-4-yl)-2,6,10,14-tetraoxapentadec-1-yl]-2,6,10,14,18,22,26,30-octaoxahentriacontan-16-yl}butanamide,
N-{(1S,2R,3R,4R,5S)-1-[(hexyloxy)methyl]-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-4-yl}acetamide,
N-[(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(2,5,8,11,14-pentaoxapentadec-1-yl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]acetamide,
N-((1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-4-yl)-2,2,2-trifluoroacetamide, compound,
N-[(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]-2,2,2-trifluoroacetamide,
N-[(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]propanamide,
N-[(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]methanesulfonamide,
N-[(1 S,2R,3R,4R,5S)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]-2,2-difluoroacetamide,
N-[(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]-3,3,3-trifluoropropanamide,
N-[(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]-N-methylacetamide,
N-[(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]-N-methylmethanesulfonamide,
tert-butyl [(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]methylcarbamate,
(1S,2R,3R,4R,5S)-1-(hydroxymethyl)-4-(methylamino)-6,8-dioxabicyclo[3.2.1]octane-2,3-diol hydrochloride,
N-[(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(15-phenyl-2,5,8,11,14-pentaoxapentadec-1-yl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]acetamide,
N-[(1S,2R,3R,4R,5S)-1-(13-azido-2,5,8,11-tetraoxatridec-1-yl)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-4-yl]acetamide,
N-[(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(2,5,8,11-tetraoxatetradec-13-en-1-yl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]acetamide,
N-[(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(2,5,8,11-tetraoxatetradec-13-yn-1-yl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]acetamide,
N-[(1S,2R,3R,4R,5S)-1-(13-amino-2,5,8,11-tetraoxatridec-1-yl)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-4-yl]acetamide,
N-[(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-(13-hydroxy-2,5,8,11-tetraoxatridec-1-yl)-6,8-dioxabicyclo[3.2.1]oct-4-yl]acetamide,
1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-oic acid,
S-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}ethanethioate,
N-{(1S,2R,3R,4R,5S)-2,3-dihydroxy-1-[13-(pyridin-2-yldisulfanyl)-2,5,8,11-tetraoxatridec-1-yl]-6,8-dioxabicyclo[3.2.1]oct-4-yl}acetamide,
N-(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)-6-(pyridin-2-yldisulfanyl)hexanamide,
N-[(1S,2R,3R,4R,5S)-1-(13-{4-[(3-[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}-2-aminopropoxy)methyl]-1H-1,2,3-triazol-1-yl}-2,5,8,11-tetraoxatridec-1-yl)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-4-yl]acetamide
hydrochloric acid salt,

6-azido-N-(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)hexanamide,
N-(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)hept-6-enamide,
N-(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)hept-6-ynamide,
7-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-7-oxoheptanoic
acid (Sodium salt),

benzyl {6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}carbamate,
6-amino-N-(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)hexanamide
acetate salt,

N-{6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamide,
N-{6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}-6-[(bromoacetyl)amino]hexanamide,
4-{[(2R)-5-(carbamoylamino)-2-{[(2R)-2-cyclopentyl-2-{[6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]amino}acetyl]amino}pentanoyl]amino}benzyl
{6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}carbamate,

N-(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)-3,19-dioxo-1-(pyridin-2-yldisulfanyl)-7,10,13,16-tetraoxa-4,20-diazahexacosan-26-amide,
N-(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)-3,31-dioxo-1-(pyridin-2-yldisulfanyl)-7,10,13,16,19,22,25,28-octaoxa-4,32-d
iazaoctatriacontan-38-amide,

N-{6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}-6-(pyridin-2-yldisulfanyl)hexanamide,
2-(pyridin-2-yldisulfanyl)ethyl {6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}carbamate,
N-{6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanamide,
N-{6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}-N?-(1,3-dihydroxypropan-2-yl)heptanediamide,
6-azido-N-{6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}hexanamide,
6-(benzyloxy)-N-{6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}hexanamide,
(1S,2R,3R,4R,5S)-4-(acetylamino)-1-{13-[4-({3-[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-bis(acetyloxy)-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-bis(acetyloxy)-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}-2-({6[(6hydroxyhexanoyl)amino]hexanoyl}amino)propoxy}methyl)-1H-1,2,3-triazol-1-yl]-2,5,8,11-tetraoxatridec-1-yl}-3-(acetyloxy)-6,8-dioxabicyclo[3.2.1]oct-2-yl
acetate,

benzyl [6-({6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}amino)-6-oxohexyl]carbamate,
6-amino-N-{6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}hexanamide
acetate,

4-(benzyloxy)-N-(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-amino-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-amino-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)butanamide,
N-(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)-4-hydroxybutanamide,
and

N-(2-{[6-({6-[(1,3-bis[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]-2-{[(1-{1-[(1S,2R,3R,4R,5S)-4-(acetylamino)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]oct-1-yl]-2,5,8,11-tetraoxatridecan-13-yl}-1H-1,2,3-triazol-4-yl)methoxy]methyl}propan-2-yl)amino]-6-oxohexyl}amino)-6-oxohexyl]oxy}-1,3-dioxan-5-yl)-6-(pyridin-2-yldisulfanyl)hexanamide
or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,227,956

SUBSTITUTED AMIDE COMPOUNDS

Pfizer Inc., New York, N...

1. A compound having Formula I

or a pharmaceutically acceptable salt thereof wherein
R1 is pyrid-2-yl, isoquinolin-1-yl or 1H-pyrrolo[2,3-c]pyridin-7-yl;

R1 is optionally mono- or di-substituted with chloro or (C1-C4)alkyl;

X and Y are independently either N or C(H), provided that at least one of X or Y is C(H);
R2 is H, fluoro, hydroxyl or methyl; R3 is


wherein R6 and R8 are each independently H, methyl, halo or (C1-C4)alkyloxy, provided that only one of R6 and R8 is halo;

wherein R10 and R11 are each independently H, (C1-C4)alkyl or (C3-C5)cycloalkyl; and

wherein R7 is hydroxyl, (C1-C4)alkyloxy, (C1-C4)alkoxycarbonyloxy(C1-C4)alkyloxy, or (C1-C4)alkylcarbonyloxy(C1-C4)alkoxy.

US Pat. No. 10,189,896

ANTIBODY TO GDF8 AND USES THEREOF

PFIZER INC., New York, N...

1. A method of detecting GDF-8 in a sample, comprising contacting a sample suspected of containing GDF-8 with a capture reagent and detecting GDF-8 in said sample, wherein the capture reagent is an antibody or antigen-binding fragment thereof that specifically binds GDF-8 comprising an antibody variable heavy (VH) region comprising the first, second and third complementarity determining regions (CDRs) from the VH region defined by the amino acid sequence of SEQ ID NO:14 or SEQ ID NO:17, and an antibody variable light (VL) region comprising the first, second and third CDRs from the VL region defined by the amino acid sequence of SEQ ID NO:16 or SEQ ID NO:18.

US Pat. No. 9,428,455

PROCESS FOR ANNEALING AMORPHOUS ATORVASTATIN

Pfizer Inc., New York, N...

1. A process for annealing amorphous atorvastatin admixed with a pharmaceutically acceptable diluent, carrier, or excipient
at elevated temperature comprising heating at ambient pressure amorphous atorvastatin in an essentially solvent-free system
wherein no additional solvent is added to a temperature of between approximately 50° C. to approximately 140° C.; holding
said temperature for approximately 30 minutes to approximately 12 hours; and cooling the resulting annealed amorphous atorvastatin.

US Pat. No. 10,188,653

DIACYLGLYCEROL ACYLTRANSFERASE 2 INHIBITORS

Pfizer Inc., New York, N...

1. A method for treating non-alcoholic fatty liver disease (NAFLD) in humans comprising the step of administering to a human in need of such treatment a therapeutically effective amount of a compound having the structure:or a pharmaceutically acceptable salt thereof.
US Pat. No. 10,188,600

STABLE LIQUID ANTIBODY FORMULATION

Pfizer Inc., New York, N...

1. A liquid composition comprising;about 2.5 mg/ml to about 20 mg/ml of an anti-NGF antibody,
about 80 mg/ml to 85 mg/ml trehalose dihydrate,
about 9.0 mM to 10.0 mM histidine buffer,
about 0.05 mg/ml to 0.1 mg/ml disodium EDTA, and
about 0.01 mg/ml to 0.15 mg/ml polysorbate 20 (PS20),
wherein the pH of said composition is from 5.8 to 6.8, wherein the antibody comprises a heavy chain variable region amino acid sequence shown in SEQ ID NO: 1, and a light chain variable region amino acid sequence shown in SEQ ID NO: 2.
US Pat. No. 9,090,690

ANTI NOTCH-1 ANTIBODIES

Pfizer Inc., New York, N...

1. An isolated antibody, or an antigen binding portion thereof, that specifically binds to human Notch-1, wherein the antibody
or antigen binding portion binds to at least a first epitope and a second epitope;
wherein the first epitope comprises 1 to 4 amino acid residues selected from amino acid residues 15, 17, 18, and 19 of SEQ
ID NO: 23; and

wherein the second epitope comprises 1 to 5 amino acid residues of SEQ ID NO: 31.
US Pat. No. 9,840,562

BINDING MOLECULES TO THE HUMAN OX40 RECEPTOR

Bristol-Myers Squibb Comp...

1. An isolated nucleic acid molecule comprising a nucleic acid sequence that encodes a binding molecule that competes for
binding to human OX40R with an antibody that comprises:
(a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7; and
(b) a light chain variable region comprising amino acid sequence of SEQ ID NO: 8.

US Pat. No. 10,071,992

DIACYLGLYCEROL ACYL TRANSFERASE 2 INHIBITORS

Pfizer Inc., New York, N...

1. A compound of Formula (I)whereinD1 and D2 are each independently N or CH;
R1 is H, or (C1-C2)alkyl optionally substituted with one or two substituents each independently selected from fluoro and (C3-C6)cycloalkyl;
R2 is H or fluoro;
R3 is,

R4 is H, cyano, or (C1-C4)alkyl optionally substituted with one or two substituents each independently selected from OH and —S(O)2R6;
R5 is H or —OH; and
R6 is (C1-C4)alkyl; or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,868,744

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

Pfizer Inc., New York, N...

1. A compound of Formula I-a:
or a pharmaceutically acceptable salt thereof, wherein:
Q1 is an N-containing 5- to 6-membered heteroaryl or an N-containing 5- to 6-membered heterocycloalkyl, each optionally substituted
with one R9 and further optionally substituted with 1, 2, 3, or 4 R10;

T1 is H, F, Cl, methyl, or C1 fluoroalkyl;

each of T2 and T3 is independently selected from the group consisting of H, halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, C3-4 cycloalkyl, C3-4 halocycloalkyl, cyclopropylmethyl, C1-4 alkoxy, C1-4 haloalkoxy;

each of R1 and R2 is independently selected from the group consisting of H, halogen, —CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, —C(?O)OH, and C(?O)—O—(C1-4 alkyl), wherein each of said C1-6 alkyl and C3-6 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from halo, —OH, —CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

each of R3 and R4 is independently selected from the group consisting of H, halogen, —OH, —NO2, —CN, —SF5, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —OC(?O)R8, —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8, wherein each of said C1-6 alkyl, C3-7 cycloalkyl, and heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the
group consisting of halogen, —CN, —OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C3-6 cycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—OR8, —C(?O)H, —C(?O)R8, —C(?O)N(R5)(R6), —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8;

or R1 and R3 together with the two carbon atoms to which they are attached form a fused N-containing 5- or 6-membered heteroaryl, a fused
N-containing 5- or 6-membered heterocycloalkyl, a fused 5- or 6-membered cycloalkyl, or a fused benzene ring, each optionally
substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, —CN, —OH, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, and C1-3 haloalkoxy;

R5 is H, C1-4 alkyl, C1-4 haloalkyl, or C3-7 cycloalkyl;

R6 is H or selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, 3, or 4 substituents each independently
selected from the group consisting of —OH, —CN, C1-4 alkyl, C3-7 cycloalkyl, C1-4 hydroxylalkyl, —S—C1-4 alkyl, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

or R5 and R6 together with the N atom to which they are attached form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl,
each optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of halogen,
—OH, oxo, —C(?O)H, —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, —CN, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy;

R7 is selected from the group consisting of H, C1-4 alkyl, and C3-7 cycloalkyl;

R8 is selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, a 4- to 14-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, or 3 substituents each independently
selected from the group consisting of halogen, —CF3, —CN, —OH, oxo, —S—C1-4 alkyl, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

R9 is halogen, C1-4 alkyl, C1-4 haloalkyl, —CN, —SF5, —N(R5)(R6), C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkoxy, or C3-7 cycloalkyl, wherein each of the C1-4 alkyl and C3-7 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting
of halogen, —N(R5)(R6), C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

each R10 is independently selected from the group consisting of halogen, —OH, —CN, —SF5, —NO2, oxo, thiono, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, —N(R5)(R6), —N(R7)(C(?O)R8), —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—R8, —SR8, and —OR8, wherein each of said C1-6 alkyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl- is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of
halogen, OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

or R9 and an adjacent R10 together with the two ring atoms on Q1 to which they are attached form a fused benzene ring or a fused 5- or 6-membered heteroaryl, each optionally substituted with
1, 2, 3, 4, or 5 independently selected R10a; and

each R10a is independently selected from the group consisting of halogen, —OH, —N(R5)(R6), —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, —CN, —SF5, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy.

US Pat. No. 9,809,579

SUBSTITUTED 3-AZABICYCLO[3.1.0]HEXANES AS KETOHEXOKINASE INHIBITORS

Pfizer Inc., New York, N...

1. A compound of Formula I

or a pharmaceutically salt thereof, wherein
Y is N or C—CN;
Z is N or CH;
X is N or CR3;

provided that at least one of Y, Z, or X is N;
R1 is C3-7cycloalkyl or a 4- to 7-membered heterocyclic moiety, wherein the heterocyclic moiety contains 1 to 2 atoms independently
selected from nitrogen, oxygen and sulfur, and wherein the cycloalkyl or heterocyclic moiety has 0 to 3 substitutuents independently
selected from —C1-3alkyl, and —OH, provided that there is no more than one —OH substituent; or

N(C1-3alkyl)2, NH(C1-3alkyl), or NH(C3-4cycloalkyl), wherein each C1-3alkyl is substituted with 0 to 1 OH;

R2 is -(L)m-CON(RN)2, -(L)m-SO2Rs, -L-(CH2)nSO2Rs, -L-(CH2)nCO2H, -L -(CH2)nC(O)Rc, -L-(CH2)nCONHSO2Rs, -L-(CH2)nSO2NHCORs, -L-(CH2)nSO2NHCONH2, or -L-(CH2)ntetrazol-5-yl;

m is 0 or 1;
n is 0 or 1;
RN is H or —C1-3alkyl;

Rs is H or —C1-3alkyl;

L is CH2, CHF, or CF2;

Rc is —C1-4alkyloxy, —C1-4alkyloxycarbonyloxy-C1-4alkyloxy, or —C1-4alkylcarbonyloxy-C1-4alkyloxy;

R3 is H, halogen, —CN, —C1-3alkyl, —OC1-3alkyl, —C1-3alkyl substituted with 1 to 3 halogen atoms, or —C3-4cycloalkyl; and

R4 is cyclopropyl, cyclobutyl, or —C1-3alkyl substituted with 0 to 5 halogen atoms as valency allows.

US Pat. No. 9,777,070

ANTI-PTK7 ANTIBODY-DRUG CONJUGATES

PFIZER INC, New York, NY...

1. An antibody-drug conjugate of the formula: Ab-(L-D), wherein:
(a) Ab is an antibody that binds to human protein tyrosine kinase 7 (PTK7) comprising at least one of a heavy chain comprising
an amino acid sequence set forth as SEQ ID NO: 37 and a light chain comprising an amino acid sequence set forth as SEQ ID
NO: 47; and

(b) L-D is a linker-drug moiety, wherein L is a linker, and D is an auristatin.

US Pat. No. 9,611,264

N-[2-(3-AMINO-2,5-DIMETHYL-1,1-DIOXIDO-5,6-DIHYDRO-2H-1,2,4-THIADIAZIN-5-YL)-1,3-THIAZOL-4-YL] AMIDES

Pfizer Inc., New York, N...

1. A compound of Formula I

wherein
R1 is a 5- to 6-membered heteroaryl, having one to four heteroatoms independently selected from N, O or S, wherein at least one
of the heteroatoms is N and wherein said N is optionally substituted with R5; and wherein said 5- to 6-membered heteroaryl is optionally substituted on carbon with one to three R4;

R2 and R3 are each independently hydrogen, C1-6alkyl, C3-6cycloalkyl or 3- to 7-membered heterocycloalkyl; wherein the C1-6alkyl is optionally substituted with a C1-3alkoxy or with one to three fluoro; and the C3-6cycloalkyl and 3- to 7-membered heterocycloalkyl are each optionally and independently substituted with one to three fluoro,
C1-3alkyl or C1-3alkoxy;

or R2 and R3, taken together with the carbon to which they are attached, form a C3-6cycloalkyl ring or 3- to 7-membered heterocycloalkyl ring, each of which is optionally and independently substituted with
one to three fluoro, C1-3alkyl or C1-3alkoxy;

R4 at each occurrence is independently selected from the group consisting of halo, hydroxy, cyano, C1-6alkyl, C1-6alkoxy, C3-6alkenyl, C3-6alkenyloxy, C3-6alkynyl, C3-6alkynyloxy, C1-6alkoxy-C1-6alkyl, C3-6cycloalkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C3-6cycloalkyl-C1-6alkoxy, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl; wherein said C1-6alkyl, C1-6alkoxy, C3-6alkenyl, C3-6alkenyloxy, C3-6alkynyl, C3-6alkynyloxy, C1-6alkoxy-C1-6alkyl, C3-6cycloalkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C3-6cycloalkyl-C1-6alkoxy, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl are each optionally substituted with one to three substituents independently selected from fluoro, chloro, hydroxy,
cyano, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy and trifluoromethoxy;
and

R5 is hydrogen or C1-6alkyl optionally substituted with one to three fluoro;

or a tautomer thereof or a pharmaceutically acceptable salt of said compound
or tautomer.
US Pat. No. 9,492,559

IMMUNOGENIC COMPOSITIONS COMPRISING CONJUGATED CAPSULAR SACCHARIDE ANTIGENS AND USES THEREOF

Pfizer Inc., New York, N...

1. An immunogenic composition comprising a Streptococcus pneumoniae serotype 22F glycoconjugate, wherein the glycoconjugate has a molecular weight of between 1000 kDa and 12,500 kDa and comprises
an isolated capsular polysaccharide from S. pneumoniae serotype 22F and a carrier protein, and wherein a ratio (w/w) of the polysaccharide to the carrier protein is between 0.4
and 2.

US Pat. No. 9,475,793

CONJUGATES AND ASSOCIATED METHODS OF PRODUCING THEM FOR THE PREVENTION OR TREATMENT OF NICOTINE ADDICTION

Pfizer Inc., New York, N...

1. A compound of formula (IIIA):

US Pat. No. 9,394,285

INDOLE AND INDAZOLE COMPOUNDS THAT ACTIVATE AMPK

Pfizer Inc., New York, N...

1. A compound of structure
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,139,561

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

Pfizer Inc., New York, N...

1. A compound selected from the group consisting of:
6-{4-[(3-cyclopropylpyridin-2-yl)oxy]-2-methylphenyl}-1,5-dimethylpyrimidine-2,4(1H,3H)-dione;
6-{4-[(3-chloro-5-methylpyridin-2-yl)oxy]-2-methylphenyl}-1,5-dimethylpyrimidine-2,4(1H,3H)-dione; and
6-(4-{[3-(difluoromethoxy)pyridin-2-yl]oxy}-2-methylphenyl)-1,5-dimethylpyrimidine-2,4(1H,3H)-dione,or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,850,301

ANTIBODY TO GDF8 AND USES THEREOF

PFIZER INC., New York, N...

1. An isolated polynucleotide comprising a nucleic acid sequence encoding at least one polypeptide chain of an antibody or
antigen binding fragment thereof that specifically binds GDF-8, said antibody or fragment comprising:
an antibody variable heavy (VH) region comprising the first, second and third complementarity determining regions (CDRs) from
the VH region defined by the amino acid sequence of SEQ ID NO:14 or SEQ ID NO:17; and

an antibody variable light (VL) region comprising the first, second and third CDRs from the VL region defined by the amino
acid sequence of SEQ ID NO:16 or SEQ ID NO:18.

US Pat. No. 9,550,795

HEXAHYDROPYRANO[3,4-D][1,3]THIAZIN-2-AMINE COMPOUNDS

Pfizer Inc., New York, N...

1. A compound selected from the group consisting of
(4aR,6R,8aS)-8a-(2-Fluorophenyl)-6-[(pyridin-2-yloxy)methyl]-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine;
(4aR,6R,8aS)-8a-(2-Fluorophenyl)-6-[(pyrazin-2-yloxy)methyl]-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine; and
(4aR,6R,8aS)-8a-(2-Fluorophenyl)-6-[(pyrimidin-2-yloxy)methyl]-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine;
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,487,581

ANTI-CTLA-4 ANTIBODY COMPOSITIONS

Pfizer Inc., New York, N...

1. A composition comprising:
a chelating agent at a concentration of about 0.01 mM to about 5.0 mM;
histidine at a concentration of about 1 mM to about 100 mM;
a surfactant at a concentration of about 0.01 mg/ml to about 10 mg/ml;
trehalose at a concentration of about 100 mM to about 300 mM; and
an antibody at a concentration of about 1 mg/ml to about 200 mg/ml, wherein said antibody binds to human CTLA-4 and comprises
the heavy chain CDR1, CDR2, and CDR3 amino acid sequences in SEQ ID NO: 2 and the light chain CDR1, CDR2, and CDR3 amino acid
sequences in SEQ ID NO: 4.

US Pat. No. 9,145,427

TRIAZINE DERIVATIVES

Pfizer Inc., New York, N...

1. A compound of the formula:
or a pharmaceutically acceptable salt thereof, in which:
A, along with X and the carbon atom to which it is attached, forms a (C6-C10)aryl or a 5- to 10-membered heteroaryl moiety, in which said aryl or heteroaryl moiety is optionally substituted with up
to 4 substituents, each independently selected from the group consisting of C3-C6 cycloalkyl, oxo, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, hydroxy, cyano, halo, —NR5R6, —C(O)—NR5R6, —NH—C(O)R5, —C(O)—OR5, —(C1-C6)alkyl-(C3-C6)cycloalkyl, a 4- to 6-membered heterocyclic moiety, phenyl, and benzyl;

X is represented by N or C, and
R5 and R6 are each optionally and independently represented by hydrogen or C1-C6 alkyl.

US Pat. No. 9,133,190

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

PFIZER INC., New York, N...

1. A method for treating a disorder in a mammal which method comprises administering to said mammal a therapeutically effective
amount of a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
each of T1, T2, T3, and T4 is independently selected from the group consisting of H, halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, cyclopropyl, fluorocyclopropyl, C1-4 alkoxy, C1-4 haloalkoxy, and —C(?O)—O—(C1-4 alkyl);

X1 is N or CH;

each of R1 and R2 is independently selected from the group consisting of H, halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and C3-4 cycloalkyl;

each of R3 and R4 is independently selected from the group consisting of H, halogen, —OH, —CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 haloalkoxy, C3-4 cycloalkyl, a 4- to 7-membered heterocycloalkyl, —N(R5)(R6), and —OR8;

each of R5 and R6 independently is H or selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, and C3-7 cycloalkyl;

or R5 and R6 together with the N atom to which they are attached form a 4- to 7-membered heterocycloalkyl or a 5-membered heteroaryl, each
optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CN,
C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy;

R8 is selected from the group consisting of C1-4 alkyl, C3-6 cycloalkyl, a 4- to 7-membered heterocycloalkyl, phenyl, and a 5- to 6-membered heteroaryl, each optionally substituted with
1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

Q1 is a moiety of

(“Moiety M1”);
Q1 or ring Q1a is an optionally substituted pyridinyl, pyrimidinyl, pyridazinyl, or pyrazinyl;

represents a single bond or double bond;
Z1 is C;

Z2 is C or N;

R9 is C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, —CN, —N(R5)(R6), C1-6 alkoxy, C1-6 haloalkoxy, or C3-7 cycloalkoxy, wherein each of the C1-4 alkyl and C3-7 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting
of halogen, —N(R5)(R6), C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

each R10 is independently selected from the group consisting of halogen, —OH, —CN, —NO2, oxo, thiono, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C2-4 alkenyl-, —N(R5)(R6), —N(R7)(C(?O)R8), —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, and —OR8, wherein each of said C1-6 alkyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C2-4 alkenyl- is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of
halogen, OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, (C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl, oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

or R9 and the adjacent R10 together with the two ring atoms on ring Q1a to which they are attached form a fused benzene ring or a fused 5- or 6-membered heteroaryl, each optionally substituted with
1, 2, 3, 4, or 5 independently selected R10a;

each R10a is independently selected from the group consisting of halogen, —OH, —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, —CN, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy; and

m is 0, 1, 2, 3, or 4,and wherein said disorder is selected from the group consisting of schizophrenia, schizoaffective disorder, cognitive impairment,
and Parkinson's disease.

US Pat. No. 9,067,934

BICYCLIC PYRIDINONES

Pfizer Inc., New York, N...

1. A compound having the structure of Formula I:
wherein:
X is a 5- to 14-membered heteroaryl containing 1-3 heteroatoms;
R1 is hydrogen, halogen, C1-6alkyl; wherein said alkyl may be optionally and independently substituted with one to three of fluoro, cyano, —CF3, hydroxy, or C1-6alkoxy;

R2a and R2b for each occurrence are each independently hydrogen, fluoro, cyano, —CF3, or C1-6alkyl; wherein said alkyl, may be optionally and independently substituted with cyano, C1-3alkyl or one to three fluoro; or R2a and R2b together with the carbon to which they are bonded form a 3- to 5-membered cycloalkyl optionally substituted with one to three
R8;

R3 is ) —(C(R11)2)t-(5- to 14-membered heteroaryl); wherein said heteroaryl moiety may be optionally independently substituted with one to five
R10;

R4a and R4b are each independently hydrogen, —CF3, or C1-6alkyl, wherein said alkyl is optionally substituted with one to three —CF3, cyano or fluoro;

R5a and R5b for each occurrence are each independently hydrogen, —CF3, or C1-6alkyl, wherein said alkyl is optionally substituted with one to three —CF3, cyano or fluoro;

R6, R7 and R8 are each independently hydrogen, —CF3, cyano, halogen, C1-6alkyl or —OR9; provided that R6 and R7 cannot both be —OH;

R9 is hydrogen or, C1-6alkyl; wherein said alkyl may be optionally and independently substituted with cyano, or one to three fluoro;

each R10 is independently hydrogen, halogen, cyano, —CF3, C1-6alkyl —(C(R11)2)m—OR12, —C(O)R13, —SF5 or —Si(CH3)3; wherein said alkyl, moieties may be optionally and independently substituted with one to three R14;

each R11 is independently hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-4cycloalkyl, fluoro, —CF3, —CHF2 or —OR12; wherein said alkyl, alkenyl, alkynyl or cycloalkyl moieties may be optionally independently substituted with one to three
fluoro or cyano;

each R12 is independently hydrogen, C1-6alkyl, or —CF3; wherein said alkyl, may be optionally independently substituted with one to three R16;

each R13 is independently C1-6alkyl; wherein said alkyl may be optionally independently substituted with one to three R16;

each R14 is independently hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, halogen, cyano, —CF3, —CHF2, —OR9 or —OCF3;

R16 is independently hydrogen, —CF3, cyano, halogen, C1-6alkyl or —OR9; wherein said alkyl moiety may be optionally substituted with one to three R17;

R17 is independently hydrogen, hydroxyl, —CF3, cyano, fluoro, C2-6alkenyl or C2-6alkynyl; wherein said alkenyl or alkynyl moiety may be optionally substituted with one to three hydrogen, fluoro or C1-6alkyl; and

each t or, m, is an integer independently selected from 0, 1, 2, 3 and 4;
z is an integer selected from 1 and 2;
y is an integer selected from 1, 2, 3 and 4;
or a pharmaceutically acceptable salt thereof.
US Pat. No. 10,124,050

IMMUNOGENIC COMPOSITIONS COMPRISING CONJUGATED CAPSULAR SACCHARIDE ANTIGENS, KITS COMPRISING THE SAME AND USES THEREOF

Pfizer Inc., New York, N...

1. A kit comprising:(a) a first immunogenic composition comprising a glycoconjugate from Streptococcus pneumoniae serotype 15B, a glycoconjugate from S. pneumoniae serotype 22F, a glycoconjugate from S. pneumoniae serotype 12F, a glycoconjugate from S. pneumoniae serotype 10A, a glycoconjugate from S. pneumoniae serotype 11A and a glycoconjugate from S. pneumoniae serotype 8; and
(b) a second immunogenic composition comprising glycoconjugates from S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, for simultaneous, concurrent, concomitant or sequential administration of the first and second immunogenic compositions.

US Pat. No. 9,518,060

SUBSTITUTED PYRROLO[3,4-C]PYRAZOLES AS PKC KINASE INHIBITORS

PFIZER INC., New York, N...

10. A pharmaceutical composition comprising an effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

US Pat. No. 9,498,443

STABLE FORMULATIONS FOR LYOPHILIZING THERAPEUTIC PARTICLES

Pfizer Inc., New York, N...

1. A lyophilized pharmaceutical composition comprising: polymeric nanoparticles comprising: a poly(lactic) acid-block-poly(ethylene)glycol
copolymer or poly(lactic)-co-poly(glycolic) acid-block-poly(ethylene)glycol copolymer, and a therapeutic agent;
a sugar; and
hydroxypropyl ?-cyclodextrin,
wherein upon reconstitution of the lyophilized pharmaceutical composition in an aqueous medium, the composition comprises
4 to 6 weight percent of the sugar; and 7 to 12 weight percent of the hydroxypropyl ?-cyclodextrin.

US Pat. No. 9,452,999

GLUCAGON RECEPTOR MODULATORS

Pfizer Inc., New York, N...

1. 3-(4-((3,3-dimethylcyclobutyl)(2-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyrimidin-5-yloxy)methyl)benzamido)propanoic acid,
Isomer 2, or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,440,949

DIACYLGLYCEROL ACYLTRANSFERASE 2 INHIBITORS

Pfizer Inc., New York, N...

11. A pharmaceutical composition comprising a compound according to any of claims 8-10 or a pharmaceutically acceptable salt of said compound, present in a therapeutically effective amount, in admixture with
at least one pharmaceutically acceptable excipient.

US Pat. No. 9,428,523

2-AMINO-6-METHYL-4,4A,5,6-TETRAHYDROPYRANO[3,4-D][1,3]THIAZIN-8A(8H)-YL-1,3-THIAZOL-4-YL AMIDES

Pfizer Inc., New York, N...

1. A pharmaceutical composition comprising a compound of Formula I
wherein
R1 is selected from the group consisting of:

phenyl optionally substituted with one to three R2;

C3-6cycloalkyl optionally substituted with one to three R2; and

a 5- to 10-membered heteroaryl, having one to four heteroatoms independently selected from N, O or S, wherein at least one
of the heteroatoms is N and wherein said N is optionally substituted with R3; and wherein said 5- to 10-membered heteroaryl is optionally substituted on carbon with one to three R2;

R2 at each occurrence is independently selected from the group consisting of halogen, hydroxy, cyano, C1-6alkyl, C1-6alkoxy, C3-6alkenyl, C3-6alkenyloxy, C3-6alkynyl, C3-6alkynyloxy, C1-6alkoxy-C1-6alkyl, C3-6cycloalkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C3-6cycloalkyl-C1-6alkoxy, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl; wherein said C1-6alkyl, C1-6alkoxy, C3-6alkenyl, C3-6alkenyloxy, C3-6alkynyl, C3-6alkynyloxy, C1-6alkoxy-C1-6alkyl, C3-6cycloalkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C3-6cycloalkyl-C1-6alkoxy, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl are each optionally substituted with one to three substituents independently selected from fluoro, chloro, hydroxy,
methyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy and trifluoromethoxy; or two
R2 groups taken together can be a C3-5alkylene; and

R3 is selected from the group consisting of hydrogen, C1-6alkyl, C3-6alkenyl, C3-6alkynyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl; wherein said C1-6alkyl, C3-6alkenyl, C3-6alkynyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl are each optionally substituted with one to three substituents independently selected from fluoro, chloro, hydroxy,
methyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy and trifluoromethoxy; or R3 and R2 taken together can be a C3-5alkylene;

or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer,
and a pharmaceutically acceptable vehicle, diluent or carrier.

US Pat. No. 9,408,922

ANTI-TOFACITINIB ANTIBODIES AND USES THEREOF FOR DRUG MONITORING

Pfizer Inc., New York, N...

1. An immunogenic tofacitinib conjugate comprising tofacitinib coupled to an immunogenic carrier, wherein the immunogenic
carrier is a protein selected from the group consisting of keyhole limpet hemocyanin and bovine serum albumin, and further
wherein
(a) the immunogenic tofacitinib conjugate has the structure

wherein BSA is bovine serum albumin; or
(b) the immunogenic tofacitinib conjugate has the structure

wherein KLH is keyhole limpet hemocyanin.

US Pat. No. 9,193,726

SUBSTITUTED PYRIDO[1,2-A]PYRAZINES FOR THE TREATMENT OF NEURODEGENERATIVE AND NEUROLOGICAL DISORDERS

Pfizer Inc., New York, N...

1. A method of reducing the production of amyloid beta proteins in a subject in need thereof, comprising:
administering to said subject a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable
salt thereof:


wherein:
X is a 5- to 14-membered heteroaryl containing 1-3 heteroatoms;
R1 is hydrogen, halogen, C1-C6alkyl, C3-C6cycloalkyl, or C2-C6alkenyl; wherein said alkyl, cycloalkyl or alkenyl is optionally substituted with one to three substituents each independently
selected from the group consisting of fluoro, hydroxy and C1-C6alkoxy;

A is a C3-C6cycloalkyl or a 4- to 10-membered heterocycloalkyl; wherein said cycloalkyl or heterocycloalkyl is optionally substituted
with one to three substituents each independently selected from the group consisting of halogen and C1-C6alkyl;

R2a and R2b for each occurrence is independently hydrogen, fluoro, cyano, C1-C6alkyl, C2-C6alkenyl, C3-C6cycloalkyl, C4-C8bicycloalkyl, C2-C6alkynyl or phenyl; wherein said alkyl, alkenyl, cycloalkyl, bicycloalkyl, alkynyl or phenyl is optionally substituted with
one to three substituents each independently selected from the group consisting of cyano, C1-C3alkyl and fluoro; or R2a and R2b together with the carbon to which they are bonded form a 3- to 5-membered cycloalkyl optionally substituted with one to three
of R8;

R3 is hydrogen, halogen, C1-C6alkyl, C2-C6alkenyl, —(C(R10)2)t—(C3-C6cycloalkyl), —(C(R10)2)t-(4- to 10-membered heterocycloalkyl), —(C(R10)2)t—(C66-C10aryl), —(C(R10)2)t-(5- to 10-membered heteroaryl) or —(C(R10)2)t—OR12; wherein said alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted with one to five
of R11;

R4a and R4b are each independently hydrogen, or C1-C6alkyl, wherein said alkyl is optionally substituted with one to three substituents each independently selected from the group
consisting of cyano and fluoro;

R5a and R5b for each occurrence are each independently hydrogen, or C1-C6alkyl, wherein said alkyl is optionally substituted with one to three substituents each independently selected from the group
consisting of cyano and fluoro;

R6, R7 and R8 are each independently hydrogen, —CF3, cyano, halogen, C1-C6alkyl, or —OR9; provided that R6 and R7 cannot both be —OH;

R9 is hydrogen, or C1-C6alkyl; wherein said alkyl is optionally substituted with one to three substituents each independently selected from the group
consisting of cyano and fluoro;

each R10 is independently hydrogen, halogen, cyano, C1-C6alkyl, or —SF5; wherein said alkyl is optionally substituted with one to three fluoro;

each R11 is independently hydrogen, halogen, —SF5, —Si(CH3)3, OR12, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, —(C(R10)2)t—(C3-C6cycloalkyl), —(C(R10)2)t—(C6-C10aryl) or —(C(R10)2)t-(5- to 10-membered heteroaryl) wherein said —Si(CH3)3, alkyl, alkenyl alkynyl, cycloalkyl, aryl or heteroaryl is optionally substituted with one to five substituents each independently
selected from the group consisting of halogen and —CF3;

each R12 is hydrogen, C1-C6alkyl, —(C(R13)2)n—(C3-C6cycloalkyl), —(C(R13)2)n-(4- to 10-membered heterocycloalkyl), —(C(R13)2)n—(C6-C10aryl), or —(C(R13)2)n-(5- to 10-membered heteroaryl); wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted
with one to five of R14;

each R13 is independently hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, halogen, cyano, —CF3, or —OCF3;

R14 is independently hydrogen, —CF3, cyano, halogen or C1-6alkyl; wherein said alkyl is optionally substituted with one to three substituents each independently selected from the group
consisting of hydroxy, cyano and fluoro;

each t or n is an integer independently selected from 0, 1, 2 or 3;
each z is 1; and
each y is an integer independently selected from 0, 1, 2, 3 or 4.
US Pat. No. 9,066,898

PROSTATE-ASSOCIATED ANTIGENS AND VACCINE-BASED IMMUNOTHERAPY REGIMENS

Pfizer Inc., New York, N...

1. A multi-antigen construct that comprises:
(a) at least one nucleotide sequence encoding an immunogenic PSA polypeptide;
(b) at least one nucleotide sequence encoding an immunogenic PSCA polypeptide; and
(c) at least one nucleotide sequence encoding an immunogenic PSMA polypeptide, wherein the immunogenic PSA polypeptide comprises
amino acids 4-240 of SEQ ID NO:17, wherein the immunogenic PSCA polypeptide comprises the amino acid sequence of SEQ ID NO:21,
and wherein the immunogenic PSMA polypeptide has at least 90% identity with amino acids 15-750 of the human PSMA of SEQ ID
NO:1 and comprises the amino acids of at least 10 conserved T cell epitopes of the human PSMA at corresponding positions.

US Pat. No. 9,950,054

GLYCOCONJUGATION PROCESSES AND COMPOSITIONS

Pfizer Inc., New York, N...

1. A method of preventing, treating or ameliorating a bacterial infection, disease or condition in a subject, comprising administering to the subject an immunologically effective amount of an immunogenic glycoconjugate composition comprising a bacterial capsular polysaccharide conjugated to a carrier protein through a (2-((2-oxoethyl)thio)ethyl)carbamate (eTEC) spacer, wherein the polysaccharide is covalently linked to the eTEC spacer through a carbamate linkage, and wherein the carrier protein is covalently linked to the eTEC spacer through an amide linkage.

US Pat. No. 9,549,929

PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES

Pfizer Inc., New York, N...

1. A method for treating a disorder or condition selected from rheumatoid arthritis, lupus, psoriasis, atopic dermatitis,
and inflammatory bowel disease, comprising the step of administering to a subject an effective amount of a composition comprising
a compound of formula I having the structure:

or a pharmaceutically acceptable salt thereof, wherein
R1 is hydrogen or C1-C4 alkyl, wherein said alkyl is further optionally substituted with one or more substituents selected from the group consisting
of halo, hydroxy, methoxy, amino, CF3, and C3-C6 cycloalkyl;

X is selected from —NH— and —CRaRb—, where (a) Ra and Rb are independently hydrogen, deuterium, C1-C6 linear or branched chain alkyl, C3-C6 cycloalkyl, aryl, (aryl)C1-C6 linear or branched chain alkyl, heteroaryl, (C1-C6 linear or branched chain alkyl)heteroaryl, (heteroaryl)C1-C6 linear or branched chain alkyl, (heterocyclic)C1-C6 linear or branched chain alkyl, or (b) Ra and Rb together form a chain comprising —(CRcRd)j—, where Rc and Rd are independently hydrogen, deuterium, C1-C6 linear or branched chain alkyl, aryl, (C1-C6 linear or branched chain alkyl)aryl, heteroaryl, (C1-C6 linear or branched chain alkyl)heteroaryl, halo, CN, CF3, hydroxyl, CONH2, or SO2CH3;

Y is -A-R5, where A is a bond, —(CH2)k— or —(CD2)k- and R5 is C1-C6 linear or branched chain alkyl, C3-C6 cycloalkyl, aryl, or —NRa?Rb?, or is an unsaturated, saturated or partially saturated monocyclic or bicyclic ring structure containing a total of four
to eleven atoms having one to three heteroatoms independently selected from the group consisting of oxygen, nitrogen, and
sulfur, wherein said alkyl, C3-C6 cycloalkyl, aryl, or monocyclic or bicyclic ring structure is further optionally substituted with one or more substituents
selected from the group consisting of deuterium, halo, C1-C6 linear or branched chain alkyl, CN, hydroxyl, CF3, —ORe, —NReRf, —S(O)pRe and C3-C6 cycloalkyl, where said alkyl and cycloalkyl may be optionally substituted with one or more substituents selected from the
group consisting of halo, CN, hydroxyl, CONH2, and SO2CH3, where (a) Ra? and Rb? are independently hydrogen, deuterium, C1-C6 linear or branched chain alkyl, C3-C6 cycloalkyl, aryl, (C1-C6 linear or branched chain alkyl)aryl, heteroaryl, or (C1-C6 linear or branched chain alkyl)heteroaryl, where said alkyl and cycloalkyl may be optionally substituted with one or more
Rc?, or (b) Ra? and Rb? together form a chain comprising —(CRc?Rd?)j—, where Rc? and Rd? are independently hydrogen, deuterium, C1-C6 linear or branched chain alkyl, aryl, (C1-C6 linear or branched chain alkyl)aryl, heteroaryl, (C1-C6 linear or branched chain alkyl)heteroaryl, halo, CN, hydroxyl, CF3, CONH2, —ORe, —NReRf, or —S(O)pRe?; where Re and Rf are independently hydrogen, deuterium, C1-C6 linear or branched chain alkyl, or C3-C6 cycloalkyl, where said alkyl and cycloalkyl may be optionally substituted with one or more substituents selected from the
group consisting of halo, CN, hydroxyl, CF3, and CONH2;

j is 2, 3, 4 or 5; k is 1, 2; 3, or 4; p is 0, 1 or 2; and,
n is 1 or 2.
US Pat. No. 9,433,687

ANTI-NOTCH3 ANTIBODIES AND ANTIBODY-DRUG CONJUGATES

Pfizer Inc., New York, N...

1. An isolated antibody, or antigen-binding fragment thereof, that binds to Notch3 comprising:
a VH CDR1, a VH CDR2, and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in
SEQ ID NO: 13; and

a VL CDR1, a VL CDR2, and a VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in
SEQ ID NO: 25.

US Pat. No. 9,402,901

VECTORS FOR EXPRESSION OF PROSTATE-ASSOCIATED ANTIGENS

Pfizer Inc., New York, N...

1. A C68 vector comprising:
(a) a C68 nucleotide sequence; and
(b) a multi-antigen construct that comprises at least one nucleotide sequence encoding an immunogenic PSA polypeptide, at
least one nucleotide sequence encoding an immunogenic PSCA polypeptide, and at least one nucleotide sequence encoding an immunogenic
PSMA polypeptide.

US Pat. No. 9,174,963

TRIAZINE COMPOUNDS AS PI3 KINASE AND MTOR INHIBITORS

Pfizer Inc., New York, N...

1. A pharmaceutically acceptable salt of a compound of the Formula I:

wherein:
R1 is


wherein:
R6, R7, R8, R9 are each independently selected from the group consisting of a hydrogen atom, and a C1-C6alkyl optionally substituted with C2-C6alkenyl, C4-C6alkadienyl, C2-C6alkynyl or C4-C6alkadiynyl;

or one of R6 and R7 or R8 and R9, together with the carbon atoms to which they are attached form an optionally substituted 5-8 membered saturated or unsaturated
ring containing 0, 1 or 2 atoms independently selected from 0, NH and S;

the dashed line - - - - - represents an optional second bond;
R2 is optionally substituted C6-C14aryl-NH—COR3, optionally substituted C1-C9heteroaryl-NH—COR3, —CH?CH—C6-C10aryl-NH—COR3 or —CH?CH—C1-C9heteroaryl-NH—COR3;

R3 is OR5, NR5R5 or NHR5;

R5 is independently selected from the group consisting of C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, optionally substituted C6-C10aryl, C1-C6haloalkyl, optionally substituted C1-C9heteroaryl, C1-C6hydroxylalkyl-, C3-C10saturated or unsaturated mono or bicyclic C3-C10cycloalkyl optionally substituted with OH, NR11R11 or 3-7 membered C1-C6heterocyclyl, and 3-10 membered saturated or unsaturated mono or bicyclic C1-C9heterocyclyl, with the proviso that three-membered cycloalkyl and heterocyclyl rings are saturated;

or two R5 groups taken together with the nitrogen atom to which they are attached form a 3 to 8 membered ring system optionally substituted
with C1-C6alkyl, which ring system is saturated or unsaturated and has, in addition to said nitrogen atom, 0 to 2 heteroatom ring members
selected from O, S, S(O), S(O)2 and NR10;

R10 is selected from the group consisting of H, C1-C6alkyl, —SO2(C1-C6alkyl), —COO(C1-C6alkyl), —CONH(C1-C6alkyl), —CON(C1-C6alkyl)2, —CO(C1-C6alkyl), and —SO2NHR11;

R11 is selected from the group consisting of H, C1-C6alkyl optionally substituted with OH, NR11R11 or a 3-7 membered C1-C6heterocyclyl, —CO(C1-C6alkyl), optionally substituted C6-C10aryl, and optionally substituted C1-C9heteroaryl;

R4 is selected from the group consisting of: a) C1-C6alkyl optionally substituted with: i) 3-10 membered C1-C9heterocyclyl optionally substituted with C1-C6alkyl-, ii) H2N—, iii) (C1-C6alkyl)NH—, iv) (C1-C6alkyl)2N—, v) NH(CH2)aN(C1-C6alkyl)2 wherein a is 2, 3 or 4, and vi) CHO, b) C3-C6alkenyl, c) C3-C6alkynyl, d) —O—C1-C8alkyl optionally substituted with —O—C1-C8alkyl, e) —O—C3-C8alkenyl, f) —O—C3-C8alkynyl, g) saturated or unsaturated mono or bicyclic C3-C8cycloalkyl, and h) saturated or unsaturated mono or bicyclic —O—C3-C12cycloalkyl, all the above optionally substituted with OH, NR11R11 or a 3-7 membered C1-C6heterocyclyl optionally substituted with C1-C6alkyl-, provided that an OH or NR11R11 is not directly bonded to a carbon atom that is double- or triple-bonded to another carbon atom; i) —CH?CH—C6-C10aryl; j) —CH?CH—C1-C9heteroaryl; k) optionally substituted C6-C10aryl; l) optionally substituted 5-10 membered C1-C9heteroaryl attached to the triazine moiety via a carbon atom; m) 3-10 membered saturated or unsaturated monocyclic C1-C9heterocyclyl attached to the triazine moiety through a carbon or nitrogen atom and optionally substituted with from 1 to 3
substituents independently selected from: OH, NR11R11, C1-C6alkyl, (C1-C6alkyl)amido-, (C1-C6alkyl)C(O)—, (C1-C6alkoxy)carbonyl-, adamantyl, C1-C6hydroxylalkyl-, (C1-C6alkyl)amido-; or a 3-7 membered C1-C6heterocyclyl, with the proviso that 3 membered heterocyclyl is saturated and attached to the triazine moiety through a nitrogen
atom, and 5 membered bicyclic heterocyclyl is saturated; n) optionally substituted —O—C6-C10aryl; o) optionally substituted —O—C1-C9heteroaryl; p) —O-(3-12 membered saturated or unsaturated mono or bicyclic)C1-C9heterocyclyl optionally substituted with (C1-C6alkoxy)carbonyl-, H2NS(O)2—, or C1-C6alkyl further optionally substituted with OH, NR11R11 or a 3-7 membered C1-C6heterocyclyl, with the proviso that three membered heterocyclyl is saturated; q) —NHC6-C10aryl, r) —NHC1-C6heteroaryl, s) —NHNH2, t) —NHNHC1-C6alkyl, u) —NHN(C1-C6alkyl)2, v) —NHOH, w) —

COOH, x) —COO—C1-C6alkyl, y) —CONR12R13, z) —NR12R13,wherein Z is CH2, 0, S(O)n or NR10 and n is 0, 1 or 2;ee) halogen, ff) C6-C14aryl-S(O)2—NH—, gg) R11NHC(O)NH—O—, and hh) optionally substituted 5-membered monocyclic C1-C4heteroaryl attached to the triazine moiety via a nitrogen atom;
R12 and R13 are each independently selected from H, optionally mono or disubstituted C1-C6alkyl, optionally substituted C3-C6alkenyl, and optionally substituted C3-C6alkynyl, the optional substituents being selected from C1-C6alkoxy, OH, NR11R11, and 3-7 membered C1-C6heterocyclyl, provided that an OH or NR11R11 is not directly bonded to a carbon atom that is double- or triple-bonded to another carbon atom;

or R12 and R13 taken together with the nitrogen atom to which they are attached form a 3 to 8 membered monocyclic ring system optionally
substituted with C1-C6alkyl, which ring system is saturated or unsaturated and has, in addition to said nitrogen atom, 0 to 2 heteroatom ring members
selected from 0, S(O)n and NR10;


or R12 and R13 taken together with the nitrogen atom to which they are attached form

wherein a and b are each independently —CH2—, O, S, or NR10, and x is 1-3;

C1-C9heteroaryl refers to a 5-10 membered aromatic ring system having one or more rings and 1, 2, 3 or 4 ring members independently
selected from O, NR10, and S(O)n;

C1-C9heterocyclyl refers to a 3-10 membered ring system having one or more rings and 1, 2, 3 or 4 ring members independently selected
from O, NR10, and S(O)n; and

optionally substituted aryl and heteroaryl groups are unsubstituted or are substituted with 1 or 2 moieties selected from
the group consisting of: a) C1-C6alkyl optionally substituted with OH, NH2, NH(C1-C6alkyl), N(C1-C6alkyl)2, —NH(CH2)wN(C1-C6alkyl)2 wherein w is 2, 3 or 4, or 3-10 membered C1-C9heterocyclyl optionally substituted with from 1 to 3 independently selected C1-C6alkyl- substituents; b) halogen; c) hydroxy; d) NH2; e) NO2; f) SO2NH2; g) COOH; h) COO(C1-C6alkyl); i) NHCOO(C1-C6alkyl); j) NH(C1-C6alkyl); k) N(C1-C6alkyl)2; l) C(O)NRaRb, wherein Ra is H or C1-C6alkyl, and Rb is H, C1-C6alkyl, (C6-C14aryl)alkyl-, or (C1-C9heteroaryl)alkyl-; m) —Y-Q, wherein Y is: i) 0, ii) NH, iii) N(C1-C6alkyl), iv) NHSO2, v) SO2NH, vi) NHCONH, vii) NHCON(C1-C6alkyl), viii) S(O)q, q is 0, 1 or 2, ix) —C(O)NH—, x) —NHC(O)— xi) —C(O)N(CH3)—, xii) C(O), or xiii) absent, and Q is selected from: i) C6-C10aryl, optionally substituted with from 1 to 3 substituents independently selected from: A) C1-C6alkoxy-optionally substituted with 1) H2N—, 2) (C1-C6alkyl)amino-, 3) di(C1-C6alkyl)amino-, 4) C1-C9heterocyclyl- optionally substituted by C1-C6alkyl-, or 5) hydroxyl, B) (C1-C6alkoxy)carbonyl-, C) (C1-C6alkoxy)C(O)NH—, D) C1-C6alkyl- optionally substituted with 1) H2N—, 2) (C1-C6alkyl)amino-, or 3) di(C1-C6alkyl)amino-, E) (C1-C6alkyl)amino-, F) di(C1-C6alkyl)amino-, G) (C1-C6alkyl)amido- optionally substituted with 1) H2N—, 2) (C1-C6alkyl)amino-, or 3) di(C1-C6alkyl)amino-, H) (C1-C6alkyl)carboxyamido-, I) C1-C9heterocyclyl-optionally substituted by C1-C6alkyl- or C1-C6hydroxylalkyl-, J) heterocyclyl(C1-C6alkyl)- optionally substituted by C1-C6alkyl-, K) halogen, L) hydroxyl, M) C1-C6hydroxylalkyl-, N) perfluoro(C1-C6)alkyl-, O) H2N—, P) O2N—, Q) H2NSO2—, R) HO2C—, and S) NC—, ii) 5-10 membered C1-C9heteroaryl, optionally substituted with from 1 to 3 substituents independently selected from: A) C1-C6alkoxy- optionally substituted with 1) H2N—, 2) (C1-C6alkyl)amino-, 3) di(C1-C6alkyl)amino-, 4) C1-C9heterocyclyl- optionally substituted by C1-C6alkyl-, or 5) hydroxyl, B) (C1-C6alkoxy)carbonyl-, C) (C1-C6alkoxy)C(O)NH—, D) C1-C6alkyl- optionally substituted with 1) H2N—, 2) (C1-C6alkyl)amino-, or 3) di(C1-C6alkyl)amino-, E) (C1-C6alkyl)amino-, F) di(C1-C6alkyl)amino-, G) (C1-C6alkyl)amido- optionally substituted with 1) H2N—, 2) (C1-C6alkyl)amino-, or 3) di(C1-C6alkyl)amino-, H) (C1-C6alkyl)carboxyamido-, I) C1-C9heterocyclyl- optionally substituted by C1-C6alkyl- or C1-C6hydroxylalkyl-, J) heterocyclyl(C1-C6alkyl)- optionally substituted by C1-C6alkyl-, K) halogen, L) hydroxyl, M) C1-C6hydroxylalkyl-, N) perfluoro(C1-C6)alkyl-, O) H2N—, P) O2N—, Q) H2NSO2—, R) HO2C—, and S) NC—, iii) 3-10 membered C1-C9heterocyclyl, optionally substituted with from 1 to 3 substituents independently selected from: A) C1-C6alkyl-, B) heterocyclyl(C1-C6alkyl)-, C) (C6-C14aryl)alkyl-, D) C1-C6acyl-, E) (C1-C6alkoxy)carbonyl-, F) (C1-C6alkyl)carboxyl-, G) halogen, H) C1-C6haloalkyl-, I) hydroxyl, J) C1-C6hydroxyalkyl-, K) H2N—, L) (C1-C6alkyl)amino-, M) di(C1-C6alkyl)amino-, N) HO2C—, O) (C1-C6alkoxy)carbonyl-, P) (C1-C6alkyl)carboxyl-, Q) (C1-C6alkyl)amido-, R) H2NC(O)—, S) (C1-C6alkyl)carboxyamido-, T) 5-10 membered C1-C9heteroaryl, U) C6-C14ary, V) C3-C6cycloalkyl W) 3-10 membered C1-C9heterocyclyl, X)NC—; and Y) —NO2; iv) C3-C10cycloalkyl, v) C1-C6alkyl, vi) C2-C6alkenyl, vii) C2-C6alkynyl, viii) C1-C6hydroxyalkyl-, ix) (CH2)vO(C1-C6alkyl), x) (CH2)vNH2, xi) (CH2)vNH(C1-C6alkyl), xii) (CH2)vN(C1-C6alkyl)2, xiii) O(CH2)vN(C1-C6alkyl)2, xiv) (CH2)vC6-C10aryl, xv) —CN, xvi) (CH2)v 5-10 membered C1-C9heteroaryl, xvii) (CH2)v 3-10 membered C1-C9heterocyclyl, optionally substituted by C1-C6alkyl-, wherein v is 1, 2, 3 or 4, and xviii) C1-C6perfluoroalkyl-; and n) C(O)Rc wherein Rc is: i) H, ii) C1-C6alkyl, or iii) C3-C6cycloalkyl,

wherein said pharmaceutically acceptable salt is selected from the group consisting of: acetate, aluminum, amsonate (4,4-diaminostilbene-2,2-disulfonate),
benzathine (N,N?-dibenzylethylenediamine), benzenesulfonate, benzoate, bicarbonate, bismuth, bisulfate, bitartrate, borate,
bromide, butyrate, calcium, calcium edetate, camsylate (camphorsulfonate), carbonate, chloride, choline, citrate, clavulariate,
diethanolamine, dihydrochloride, diphosphate, edetate, edisylate (camphorsulfonate), esylate (ethanesulfonate), ethylenediamine,
fumarate, gluceptate (glucoheptonate), gluconate, glucuronate, glutamate, hexafluorophosphate, hexylresorcinate, hydrabamine
(N,N?-bis(dehydroabietyl)ethylenediamine), hydrobromide, hydrochloride, hydroxynaphthoate, 1-hydroxy-2-naphthoate, 3-hydroxy-2-naphthoate,
iodide, isothionate (2-hydroxyethanesulfonate), lactate, lactobionate, laurate, lauryl sulfate, lithium, magnesium, malate,
maleate, mandelate, meglumine (1-deoxy-1-(methylamino)-D-glucitol), mesylate, methyl bromide, methylnitrate, methylsulfate,
mucate, napsylate, nitrate, N-methylglucamine ammonium salt, oleate, oxalate, palmitate, pamoate (4,4?-methylenebis-3-hydroxy-2-naphthoate,
or embonate), pantothenate, phosphate, picrate, polygalacturonate, potassium, propionate, p-toluenesulfonate, salicylate,
sodium, stearate, subacetate, succinate, sulfate, sulfosaliculate, suramate, tannate, tartrate, teoclate (8-chloro-3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione),
triethiodide, tromethamine (2-amino-2-(hydroxymethyl)-1,3-propanediol), valerate, and zinc salts.

US Pat. No. 9,145,416

N1-PYRAZOLOSPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS

Pfizer Inc., New York, N...

1. A compound of Formula (I)
or a pharmaceutically acceptable salt thereof; wherein
R1 is (C1-C6)alkyl, (C3-C7)cycloalkyl, tetrahydrofuranyl or oxetanyl; wherein said (C1-C6)alkyl is optionally substituted with 1 to 3 substituents independently selected from (C1-C3)alkoxy, hydroxy, fluoro, phenyl, tetrahydrofuranyl or oxetanyl;

R2 is hydrogen, halo, (C1-C3)alkyl, or cyano;

R3 are each independently hydrogen or (C1-C3)alkyl;

L is a direct bond or a (C1-C6)alkylene wherein one carbon of the (C1-C6)alkylene is optionally replaced by —C(O)—, —C(O)NH—, —NHC(O)—, —O—, —S—, NH or N(C1-C3)alkyl;

Z is CH2 or O;

A1 and A2 are each independently (C6-C10)aryl, 5 to 12 membered heteroaryl or 8 to 12 membered fused heterocyclicaryl; wherein said (C6-C10)aryl, 5 to 12 membered heteroaryl or 8 to 12 membered fused heterocyclicaryl are each optionally substituted with one to
three substituents independently selected from (C1-C3)alkyl, (C1-C3)alkoxy, halo, amino, (C1-C3)alkylamino, di(C1-C3)alkylamino, hydroxy, cyano and amido wherein the alkyl portion of the (C1-C3)alkyl, (C1-C3)alkoxy, (C1-C3)alkylamino and di(C1-C3)alkylamino are optionally substituted with one to five fluoro; and wherein one of A1 or A2 is substituted by CO2R4 or (C1-C6)CO2R4; and

R4 is H.

US Pat. No. 9,138,486

CYTOTOXIC PEPTIDES AND ANTIBODY DRUG CONJUGATES THEREOF

Pfizer Inc., New York, N...

1. A method of treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of
the compound of formula I:

or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence,
W is

R1 is hydrogen, C1-C8 alkyl or C1-C8 haloalkyl;

R2 is hydrogen, C1-C8 alkyl or C1-C8 haloalkyl;

R3A and R3B are either of the following:

(i) R3A is hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C3-C8 carbocyclyl, C1-C10 heterocyclyl, aryl, heteroaralkyl, halogen or aralkyl; and R3B is C1-C8 alkyl, C1-C8 haloalkyl, C3-C8 carbocyclyl, C1-C10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; or

(ii) R3A and R3B taken together are C2-C8 alkylene or C1-C8 heteroalkylene;

R4A and R4B are either of the following:

(i) R4A is hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C3-C8 carbocyclyl, C1-C10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and R4B is hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C3-C8 carbocyclyl, C1-C10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or

(ii) R4A and R4B taken together are C2-C8 alkylene or C1-C8 heteroalkylene;

R5 is

C1-C10 heterocyclyl, C3-C8 carbocycly or C6-C14 aryl, optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of —C1-C8 alkyl, —C1-C8 alkyl-N(R?)2, —C1-C8 alkyl-C(O)R?, —C1-C8 alkyl-C(O)OR?—O—(C1-C8 alkyl), —C(O)R?, —OC(O)R?, —C(O)OR?, —C(O)N(R?)2, —NHC(O)R?, —S(O)2R?, —S(O)R?, —OH, halogen, —N3, —N(?)2, —CN, —NHC(?NH)NH2, —NHCONH2, —S(?O)2R? and —SR?, wherein each R? is independently selected from the group consisting of hydrogen, C1-C8 alkyl and unsubstituted aryl, or two R? can, together with the nitrogen to which they are attached, form a C1-C10 heterocyclyl; or R5 is
optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of C1-C8 alkyl, —C1-C8 alkyl-N(R?)2, —C1-C8 alkyl-C(O)R?, —C1-C8 alkyl-C(O)OR?, —O—(C1-C8 alkyl), —C(O)R?, —OC(O)R?, —C(O)OR?, —C(O)N(R?)2, —NHC(O)R?, —S(O)2R?, —S(O)R?, —OH, halogen, —N3, —N(R?)2, —CN, —NHC(?NH)NH2, —NHCONH2, —S(?O)2R?, —SR? and arylene-R?, wherein each R? is independently selected from the group consisting of hydrogen, C1-C8 alkyl, C1-C8heterocyclyl, C1-C10alkylene-C3-C8heterocyclyl and aryl, or two R? can, together with the nitrogen to which they are attached, form a C1-C10 heterocyclyl; R6 is hydrogen, —C1-C8 alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl or —C1-C8 haloalkyl;
R12 is hydrogen, C1-C4 alkyl, C1-C10 heterocyclyl or C6-C14 aryl;

R13 is C1-C10 heterocyclyl; and

X is O or S;
provided that when R3A is hydrogen X is S.

US Pat. No. 9,073,852

SALT FORMS OF [R-(R*,R*)]-2-(4-FLUOROPHENYL)-BETA,DELTA-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1-HEPTANOIC ACID

Pfizer Inc., New York, N...

1. An atorvastatin morpholine having an x-ray powder diffraction pattern containing the following 2? peaks measured using
CuK? radiation: 9.7, 16.0, 18.9, 19.6, 20.8, 22.1, 23.9, and 25.0, or a solid state 19F nuclear magnetic resonance having the following chemical shifts expressed in parts per million: ?117.6.
US Pat. No. 9,579,386

DRUG LOADED POLYMERIC NANOPARTICLES AND METHODS OF MAKING AND USING SAME

Pfizer Inc., New York, N...

1. A therapeutic nanoparticle comprising:
about 4 to about 25 weight percent of a therapeutic agent;
about 10 to about 99 weight percent of a diblock poly(lactic) acid-poly(ethylene)glycol copolymer comprising poly(lactic)
acid having a number average molecular weight of about 15 to 20 kDa, and poly(ethylene)glycol having a number average molecular
weight of about 4 to 6 kDa;

wherein the hydrodynamic diameter of the therapeutic nanoparticle is about 60 nm to about 140 nm; and
wherein the therapeutic nanoparticles releases less than 2% of the therapeutic agent over about one minute when placed in
a phosphate buffer solution at 37° C.

US Pat. No. 9,540,352

SUBSTITUTED 1,7-NAPHTHYRIDINES AS DOPAMINE D1 LIGANDS

Pfizer Inc., New York, N...

15. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

US Pat. No. 9,458,168

BICYCLIC-FUSED HETEROARYL OR ARYL COMPOUNDS

Pfizer Inc., New York, N...

1. A compound of Formula Ia,

wherein
X and X? are each CR8; Y is N or —N+—O?;

R1 is C1-C6alkyl; wherein said alkyl is optionally substituted with one to five halogen, deuterium, —OR5, —SR5, —NR11aR11b, cyano, C1-C6alkyl, C3-C6cycloalkyl or —C1-C6alkoxy;

R2 is (CR3aR3b)m-(3- to 10-membered cycloalkyl); —(CR3aR3b)m-(3- to 10-membered heterocycloalkyl) having one to three heteroatoms; —(CR3aR3b)m-(5- to 10 membered heteroaryl) having one to three heteroatoms; or —(CR3aR3b)m—C6-C12aryl; wherein said cycloalkyl, heterocycloalkyl, heteroaryl or aryl is optionally substituted with one to five R4; and wherein, if the heteroatom on said heterocycloalkyl and heteroaryl is N, said N is optionally substituted with R4?; or R2 is C1-C6alkyl, wherein said alkyl is optionally substituted with NH2, OH or cyano;

R3a and R3b for each occurrence are independently hydrogen or C1-C3alkyl;

R4 for each occurrence is independently a bond, deuterium halogen, cyano, C1-C6alkyl, C2-C6alkenyl, oxo —OR5, —SR5, —S(O)R9, —S(O)2R9, —NR11aR11b, —C(O)R10, —(CR3aR3b)n-(3- to 7- membered cycloalkyl), —(CR3aR3b)n-(4- to 10- membered heterocycloalkyl), having one to three heteroatoms, —(CR3aR3b)n-(5- to 10 membered heteroaryl), having one to three heteroatoms, or —(CR3aR3b)n—C6-C12aryl wherein said alkyl, cycloalkyl, heterocycloalkyl, heteroaryl or aryl is each optionally and independently substituted
with one to five deuterium, halogen, OR5, —SR5, —NR11aR11b, cyano, C1-C6alkyl, C3-C6cycloalkyl or —C1-C6alkoxy; or two R4 taken together with the respective carbons to which each are bonded form a 3- to 6-membered cycloalkyl or 4- to 6-membered
heterocycloalkyl, wherein said cycloalkyl or heterocycloalkyl is optionally substituted with one to three halogen, deuterium,
—OR5, —SR5, —NR11aR11b, cyano or C1-C6alkyl or C1-C6alkoxy, wherein the alkyl or alkoxy is optionally substituted with halogen, deuterium, —OR5, —SR5, —NR11aR11b or cyano; and wherein, if a heteroatom on said heterocycloalkyl is N, said N is optionally substituted with R4?;

R4? is independently C1-C6alkyl, C2-C6alkenyl, —C(O)R10, —S(O)2R9, —(CR3aR3b)n-(3- to 7- membered cycloalkyl), —(CR3aR3b)n-(4- to 10- membered heterocycloalkyl) or C(O)(CH2)tCN; wherein said alkyl, alkenyl, cycloalkyl, or heterocycloalkyl is each optionally and independently substituted with one
to five deuterium, halogen, OH, cyano or C1-C6alkoxy; or R4 and R4? taken together with the respective atoms to which each are bonded form a 3- to 6-membered cycloalkyl or 4- to 6-membered
heterocycloalkyl, wherein said cycloalkyl or heterocycloalkyl is optionally substituted with one to three halogen, deuterium,
—OR5, —SR5, —NR11aR11b, cyano, C1-C6alkyl or C1-C6alkoxy, wherein the alkyl or alkoxy is optionally substituted with halogen, deuterium, —OR5, —SR5, —NR11aR11b, or cyano;

R5 is independently hydrogen or C1-C6alkyl, wherein said alkyl is optionally substituted with halogen, deuterium, C1-C6alkoxy, C1-C6alkylthiolyl, —NR11aR11b, cyano, C1-C6alkyl or C3-C6cycloalkyl; or two R5 taken together with the oxygen atoms to which they are bonded form a 5- or 6-membered heterocycloalkyl;

R6 is —C(O)NHR7, CO2R7 or cyano;

R7 is hydrogen or C1-C6alkyl;

each R8 is independently hydrogen, halogen, cyano, —OR5, —SR5, —NR11aR11b, C1-C6alkyl, C3-C6cycloalkyl, 3- to 10-membered heterocycloalkyl or 5- to 6-membered heteroaryl or aryl, wherein said alkyl, cycloalkyl, heterocycloalkyl,
heteroaryl or aryl is optionally substituted with one to three halogen, —NR11aR11b, OR5, —SR5, cyano, C1-C3 alkyl, —C(O)R10 or oxo;

R8? is hydrogen, deuterium, halogen, cyano, —OR5, —SR5, or NR11aR11b;

R9 is —(CR3aR3b)p—(C1-C3alkyl), —(CR3aR3b)p-(4- to 6- membered cycloalkyl), —(CR3aR3b)p—(4- to 6- membered heterocycloalkyl) or —(CR3aR3b)p—(C5-C9aryl), wherein said alkyl, cycloalkyl, heterocycloalkyl or aryl are each optionally substituted with fluoro or C1-C3alkyl;

R10 is C1-C6alkyl, wherein said alkyl is optionally substituted with deuterium, halogen, OH, C1-C6alkoxy or cyano;

R11a and R11b are each independently hydrogen or C1-C6alkyl, wherein said alkyl is optionally substituted with deuterium, C1-C6alkoxy or cyano; and if C2-C6alkyl, said alkyl is optionally substituted with deuterium, C1-C6alkoxy, cyano, halogen or OH;

m is independently 0, 1, 2 or 3;
n is independently 0, 1, 2 or 3;
p is independently 0 or 1; and
t is 1, 2 or 3;
or a pharmaceutically acceptable salt of said compound or a tautomer of said compound or said salt.
US Pat. No. 9,439,901

DIOXA-BICYCLO[3.2.1]OCTANE-2,3,4-TRIOL DERIVATIVES

Pfizer Inc., New York, N...

1. A method for treating obesity in humans comprising the step of administering to a human in need of such treatment a therapeutically
effective amount of a pharmaceutical composition comprising: (i) (1S,2S,3S,4R,5S)-5-[-4-chloro-3-(4-ethoxy-benzyl)-phenyl]-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol;
(ii) a pharmaceutically acceptable excipient, diluent, or carrier and (iii) sitagliptin; or a pharmaceutically acceptable
salt thereof.
US Pat. No. 9,370,516

USE OF GHRELIN RECEPTOR INVERSE AGONISTS OR ANTAGONISTS FOR TREATING SLEEP DISORDERS

Pfizer Inc., New York, N...

1. A method of treating a sleep disorder in a patient comprising the step of administering to the patient, in need of such
treatment, a therapeutically effective amount of (R)-2-(2-methylimidazo[2,1-b]thiazol-6-yl)-1-(2-(5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonan-7-yl)ethanone,
or a pharmaceutically acceptable salt thereof, wherein the sleep disorder is primary insomnia.

US Pat. No. 9,056,834

GLUCAGON RECEPTOR MODULATORS

Pfizer Inc., New York, N...

1. A compound of Formula I

or a pharmaceutically acceptable salt thereof, wherein
R1 is phenyl substituted with halo or trifluoromethyl;

or a 6-membered heteroaryl group which is optionally fused with a (C4-C7)cycloalkyl, phenyl or 5 to 6 membered heteroaryl, and wherein the optionally fused 6-membered heteroaryl group is optionally
substituted with one to four substituents each independently selected from halo, —S(O)2—(C1-3)alkyl, hydroxy, —C(O)NRaRb, cyano, (C1-C6)alkyl optionally substituted with one to three fluoro, or (C1-C6)alkoxy optionally substituted with one to three fluoro;

Ra and Rb are each independently H or (C1-C3)alkyl;

R2 is H;

R3 is —(CH2)2CO2H;

A1, A2, A3 and A4 are each CR4;

R4 at each occurrence is independently H, halo, cyano, (C1-C3)alkyl optionally substituted with one to three fluoro, or (C1-C3)alkoxy optionally substituted with one to three fluoro;

L is —CH(R5)—X—;

X is NH;
R5 is (C1-C6)alkyl which is optionally substituted with one to three fluoro, hydroxy or methoxy; (C3-C7)cycloalkyl which is optionally substituted with one to two (C1-C3)alkyl which are optionally substituted with one to three fluoro or one to two (C1-C3)alkyl and wherein one to two carbons of the (C3-C7)cycloalkyl can be replaced with a NH, N(C1-C3)alkyl, O or S; or (C3-C7)cycloalkyl-(C1-C6)alkyl wherein the (C3-C7)cycloalkyl group of said (C3-C7)cycloalkyl-(C1-C6)alkyl is optionally substituted with one to two (C1-C3)alkyl which are optionally substituted with one to three fluoro;

B1, B2, B3 and B4 are each independently CR6 or N, with the proviso that one of B1, B2, B3 and B4 is N and the remaining are CR6; and

R6 at each occurrence is independently H, halo, (C1-C3)alkyl optionally substituted with one to three fluoro, or (C1-C3)alkoxy optionally substituted with one to three fluoro.

US Pat. No. 10,004,317

DUAL-ENDED LIP BALM CONTAINER

Pfizer Inc., New York, N...

1. A lip balm applicator comprising:a cap comprising
a cap top with a cap flat edge and a cap top perimeter,
a cap exterior,
a cap interior having a lower cap interior and an upper cap interior,
a first cap engagement assembly on the cap interior, and
a cap bottom perimeter;
wherein the cap has three to six sides;
a liner comprising
a domed upper liner section,
a lower liner section with a liner perimeter which contains a second cap engagement assembly which aligns with the first cap engagement assembly and engages the liner perimeter with the lower cap interior,
a liner exterior,
a liner interior having a lower liner interior and an upper liner interior, and
a first liner engagement assembly on the lower liner interior, and
a base comprising
an upper base section having a base top edge,
a lower base section,
a partition dividing the upper base section and the lower base section and extending to a base perimeter which aligns with the cap bottom perimeter,
the partition having a partition bottom and a partition top, with the partition top having an outer partition top section and an inner partition top section,
an aperture in the partition,
an upper base section exterior wall comprising a second liner engagement assembly which aligns with the first liner engagement assembly and engages the lower liner interior with the upper base section exterior wall,
an upper base section interior wall,
a plurality of stabilizers arising from a first area adjacent to the upper base section interior wall on the inner partition top section, rising to a level at or near horizontal with the base top edge and extending radially inward to a second area overhanging the aperture,
a gap between each stabilizer and the upper base section interior wall, and
a base engagement assembly on the lower base section which provides releasable engagement of the lower base section on the lip balm applicator with a lower base section on a second lip balm applicator;
wherein the base has three to six sides and corresponds to the three to six sides of the cap;
and wherein the lip balm applicator has three to six sides and corresponds to the three to six sides of the cap.

US Pat. No. 9,856,263

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

PFIZER INC., New York, N...

1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
L1 is O, S, NRN, C(?O), or CH(OH);

Q1 is an N-containing 5- to 10-membered heteroaryl, an N-containing 4- to 12-membered heterocycloalkyl, or phenyl, wherein each
of the heteroaryl, heterocycloalkyl, or phenyl is optionally substituted with one R9 and further optionally substituted with 1, 2, 3, or 4 R10;

X1 is N or C-T1;

X2 is N or C-T2;

X3 is N or C-T3;

X4 is N or C-T4;

provided that at most two of X1, X2, X3, and X4 are N;

each of T1, T2, T3, and T4 is independently selected from the group consisting of H, halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, C3-4 cycloalkyl, C3-4 halocycloalkyl, cyclopropylmethyl, C1-4 alkoxy, C1-4 haloalkoxy;

T5 is H, F, Cl, methyl, or C1 fluoroalkyl;

RN is H, C1-4 alkyl, C3-4 cycloalkyl, or —C1-2 alkyl-C3-4 cycloalkyl,

each of R1 and R2 is independently selected from the group consisting of H, halogen, —CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, —C(?O)OH, and C(?O)—O—(C1-4 alkyl), wherein each of said C1-6 alkyl and C3-6 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from halo, —OH, —CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

each of R3 and R4 is independently selected from the group consisting of H, halogen, —OH, —NO2, —CN, —SF5, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —OC(?O)R8, —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8, wherein each of said C1-6 alkyl, C3-7 cycloalkyl, and heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the
group consisting of halogen, —CN, —OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C3-6 cycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—OR8, —C(?O)H, —C(?O)R8, —C(?O)N(R5)(R6), —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8;

or R1 and R3 together with the two carbon atoms to which they are attached form a fused N-containing 5- or 6-membered heteroaryl, a fused
N-containing 5- or 6-membered heterocycloalkyl, a fused 5- or 6-membered cycloalkyl, or a fused benzene ring, each optionally
substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, —CN, —OH, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, and C1-3 haloalkoxy;

R5 is H, C1-4 alkyl, C1-4 haloalkyl, or C3-7 cycloalkyl;

R6 is H or selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, 3, or 4 substituents each independently
selected from the group consisting of —OH, —CN, C1-4 alkyl, C3-7 cycloalkyl, C1-4 hydroxylalkyl, —S—C1-4 alkyl, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

or R5 and R6 together with the N atom to which they are attached form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl,
each optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of halogen,
—OH, oxo, —C(?O)H, —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, —CN, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy;

R7 is selected from the group consisting of H, C1-4 alkyl, and C3-7 cycloalkyl;

R8 is selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, a 4- to 14-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, or 3 substituents each independently
selected from the group consisting of halogen, —CF3, —CN, —OH, oxo, —S—C1-4 alkyl, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

R9 is halogen, C1-4 alkyl, C1-4 haloalkyl, —CN, —SF5, —N(R5)(R6), C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkoxy, or C3-7 cycloalkyl, wherein each of the C1-4 alkyl and C3-7 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting
of halogen, —N(R5)(R6), C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

each R10 is independently selected from the group consisting of halogen, —OH, —CN, —SF5, —NO2, oxo, thiono, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)—C1-4 alkyl-, —N(R5)(R6), —N(R7)(C(?O)R8), —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR8, and —OR8, wherein each of said C1-6 alkyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl- is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of
halogen, OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

or R9 and an adjacent R10 together with the two ring atoms on Q1 to which they are attached form a fused benzene ring or a fused 5- or 6-membered heteroaryl, each optionally substituted with
1, 2, 3, 4, or 5 independently selected R10a; and

each R10a is independently selected from the group consisting of halogen, —OH, —N(R5)(R6), —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, —CN, —SF5, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy,
with the proviso that
(1) when L1 is NRN, then X2 is CT2; and

(2) when L1 is O, X2 is N, then Q1 is not an optionally substituted tetrazolyl group.

US Pat. No. 9,751,937

ANTAGONIST ANTIBODIES AGAINST GDF-8 AND USES THEREFOR

PFIZER INC., New York, N...

1. A method of increasing the mass or strength of a muscle of a mammal, comprising administering to a mammal a therapeutically
effective amount of an antibody or antigen binding fragment thereof that specifically binds GDF-8, said antibody or fragment
comprising:
an antibody variable heavy (VH) region comprising first, second and third complementarity determining regions (CDR), wherein
VH CDR1 comprises SEQ ID NO:10 or SEQ ID NO:20, VH CDR2 comprises SEQ ID NO:11 or SEQ ID NO:21, and VH CDR3 comprises SEQ
ID NO:12; and

an antibody variable light (VL) region comprising first, second and third complementarity determining regions (CDR), wherein
VL CDR1 comprises SEQ ID NO:13, VL CDR2 comprises SEQ ID NO:14, and VL CDR3 comprises SEQ ID NO:15;

wherein said VH region comprises leucine at the amino acid position corresponding to residue number 111 of SEQ ID NO:44 (Kabat
position 108).

US Pat. No. 9,517,274

GLYCOCONJUGATION PROCESSES AND COMPOSITIONS

Pfizer Inc., New York, N...

1. A method of making a glycoconjugate comprising a saccharide conjugated to a carrier protein through a (2-((2-oxoethyl)thio)ethyl)carbamate
(eTEC) spacer, comprising the steps of:
a) reacting a saccharide with 1,1?-carbonyl-di-(1,2,4-triazole) (CDT) or 1,1?-carbonyldiimidazole (CDI), in an organic solvent
to produce an activated saccharide;

b) reacting the activated saccharide with cystamine or cysteamine or a salt thereof, to produce a thiolated saccharide;
c) reacting the thiolated saccharide with a reducing agent to produce an activated thiolated saccharide comprising one or
more free sulfhydryl residues;

d) reacting the activated thiolated saccharide with an activated carrier protein comprising one or more ?-haloacetamide groups,
to produce a thiolated saccharide-carrier protein conjugate; and

e) reacting the thiolated saccharide-carrier protein conjugate with (i) a first capping reagent capable of capping unconjugated
?-haloacetamide groups of the activated carrier protein; and/or (ii) a second capping reagent capable of capping unconjugated
free sulfhydryl residues;

whereby an eTEC linked glycoconjugate is produced.

US Pat. No. 9,198,917

HEXAHYDROPYRANO[3,4-D][1,3]THIAZIN-2-AMINE COMPOUNDS

Pfizer Inc., New York, N...

1. A method of treating Alzheimer's disease in a patient, the method comprising administering a therapeutically effective
amount of a compound of Formula I,
Wherein
R1 is hydrogen or methyl, wherein said methyl is optionally substituted with one to three substituents independently selected
from halogen or methoxy;

R2 is C1-6 alkyl, —(C(R5)2)m—(C3-6 cycloalkyl), —(C(R5)2)m—(C6-10 aryl), —(C(R5)2)m-(5- to 10-membered heteroaryl) or —(C(R5)2)t—OR6; wherein said alkyl, cycloalkyl, aryl or heteroaryl moieties are optionally substituted with one to three substituents independently
selected from halogen, C1-6 alkyl, —CH2F, —CHF2, —CF3, —CN or —OR7;

R3 is —(C(R5)2)m—(CN) or —(C(R5)2)n—(NHR7);

R4 is independently selected from halogen, C1-6 alkyl or C1-6 alkoxy; wherein said alkyl or alkoxy is optionally substituted with one to three fluoro;

R5 at each occurrence is independently selected from hydrogen or C1-3 alkyl, wherein said alkyl is optionally substituted with one to three halogen;

R6 is hydrogen, C1-6 alkyl or —(C(R5)2)n—(C6-10 aryl), wherein said alkyl and aryl are optionally substituted with one to three substituents independently selected from halogen,
C1-3 alkyl, —CH2F, —CHF2, —CF3, —CN or —OH;

R7 for each occurrence is hydrogen or C1-6 alkyl, wherein said alkyl is optionally substituted with one to three substituents independently selected from halogen or
C1-6 alkoxy;

m at each occurrence is independently 0, 1 or 2;
n at each occurrence is independently is 1 or 2;
t is 1 or 2; and
x is 0, 1, 2 or 3;
or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer;to a patient in need of treatment thereof.
US Pat. No. 10,028,962

2-AMINO-6-METHY1-4,4A,5,6-TETRAHYDROPYRANO[3,4-D][1,3]THIAZIN-8A(8H)-YL-1,3-THIAZOL-4-YL AMIDES

Pfizer Inc., New York, N...

1. A method of treating Alzheimer's disease in a patient, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical combination, the pharmaceutical combination comprising a compound selected from the group consisting ofN-{2-[(4aR,6S,8aR)-2-Amino-6-methyl-4,4a,5,6-tetrahydropyrano [3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-(difluoromethoxy)pyridine-2-carboxamide;
N-{2-[(4aR,6S,8aR)-2-Amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-(difluoromethoxy) pyrazine-2-carboxamide;
N-{2-[(4aR,6S,8aR)-2-Amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-chloropyridine-2-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-fluoropyridine-2-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-(difluoromethoxy)-3-methylpyridine-2-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-(difluoromethoxy)-3-methylpyrazine-2-carboxamide; and
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-3-chloro-5-(difluoromethoxy)pyridine-2-carboxamide; or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer; and one or more additional pharmaceutical agent.
US Pat. No. 9,861,638

SALTS AND POLYMORPHS OF 8-FLUORO-2-{4-[(METHYLAMINO)METHYL]PHENYL}-1,3,4,5-TETRAHYDRO-6H-AZEPINO[5,4,3-CD]INDOL-6-ONE

PFIZER INC., New York, N...

1. A method of inhibiting poly(ADP-ribose) polymerase (PARP) activity in a mammal having a BRCA1 and/or BRCA2 mutation, wherein
the mammal has ovarian cancer, the method comprising administering to a mammal in need thereof a therapeutically effective
amount of a pharmaceutical composition comprising a salt selected from the group consisting of a camsylate salt of 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one
and a maleate salt of 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one and a
pharmaceutically acceptable carrier.

US Pat. No. 9,844,509

HIGH THROUGHPUT FABRICATION OF NANOPARTICLES

PFIZER INC., New York, N...

1. A method of preparing nanoparticles comprising:
(a) providing:
(i) a first stock solution comprising an active agent and polymers admixed with one or more organic solvents;
(ii) a second stock solution comprising a surfactant and a solvent in aqueous phase;
(iii) a third stock solution comprising a water or buffer quench solution; and
(iv) a fourth stock solution comprising an aqueous carrier and beta-cyclodextrin;
(b) combining a volume of said first stock solution and a volume of said second stock solution to form an emulsification solution;
(c) emulsifying said emulsification solution;
(d) combining the emulsion formed in step (c) with a volume of the third stock solution; and
(e) adding a volume of the fourth stock solution to the solution formed in step (d); and separating beta-cyclodextrin and
dissolved unencapsulated active agent from the resulting solution.

US Pat. No. 9,744,133

ENHANCED STABILITY OF NOVEL LIQUID COMPOSITIONS

Pfizer Inc., New York, N...

1. A liquid oral pharmaceutical composition comprising:
(i) from about 0.1% to about 20% w/v polyvinylpyrrolidone;
(ii) from about 5% to about 70% w/v polyethylene glycol;
(iii) from about 1% to about 30% w/v propylene glycol;
(iv) from about 1% to 10% w/v guaifenesin; and
(v) from about 0.01% to about 1.0% w/v phenylephrine;
further comprising one or more additional pharmaceutical agent selected from the group consisting of analgesics, decongestants,
expectorants, antitussives, antipyretics, anti-inflammatory agents, cough suppressants, and antihistamines; and wherein the
composition comprises about less than 2% total phenylephrine degradants, as a percent weight over weight phenylephrine, and
about less than 2% loss of phenylephrine from the initial total phenylephrine content, measured over a 3 month time period
while stored at 40° C. and 75% relative humidity.

US Pat. No. 9,745,317

HETEROCYCLIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

Pfizer Inc., New York, N...

4. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
n is 1 or 2;
L1 is O, S, NRN, C(?O), or CH(OH);

Q1 is an N-containing 5- to 6-membered heteroaryl or an N-containing 5- to 6-membered heterocycloalkyl, each optionally substituted
with one R9 and further optionally substituted with 1, 2, 3, or 4 R10;

X1 is O, S, NH, N(C1-4 alkyl), N(cyclopropyl), N(—CH2-cyclopropyl), or C(T2)2;

X2 is C(T2)2;

X3 is C(T3)2;

X4 is C-T4;

T1 is H, F, CI, methyl, or C1 fluoroalkyl;

each T2 is independently selected from the group consisting of H, halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, C3-4 cycloalkyl, C3-4 halocycloalkyl, cyclopropylmethyl, C1-4 alkoxy, C1-4 haloalkoxy;

each T3 is independently selected from the group consisting of H, —OH, halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, C3-4 cycloalkyl, C3-4 halocycloalkyl, cyclopropylmethyl, C1-4 alkoxy, C1-4 haloalkoxy;

T4 is selected from the group consisting of H, halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, C3-4 cycloalkyl, C3-4 halocycloalkyl, cyclopropylmethyl, C1-4 alkoxy, C1-4 haloalkoxy;

RN is H, C1-4 alkyl, C3-4 cycloalkyl, or —C1-2 alkyl-C3-4 cycloalkyl,

each of R1 and R2 is independently selected from the group consisting of H, halogen, —CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, —C(?O)OH, and C(?O)—O—(C1-4 alkyl), wherein each of said C1-6 alkyl and C3-6 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from halo, —OH, —CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

each of R3 and R4 is independently selected from the group consisting of H, halogen, —OH, —NO2, —CN, —SF5, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —OC(?O)R8, —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8, wherein each of said C1-6 alkyl, C3-7 cycloalkyl, and heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the
group consisting of halogen, —CN, —OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C3-6 cycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—OR8, —C(?O)H, —C(?O)R8, —C(?O)N(R5)(R6), —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8;

or R1 and R3 together with the two carbon atoms to which they are attached form a fused N-containing 5- or 6-membered heteroaryl, a fused
N-containing 5- or 6-membered heterocycloalkyl, a fused 5- or 6-membered cycloalkyl, or a fused benzene ring, each optionally
substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, —CN, —OH, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, and C1-3 haloalkoxy;

R5 is H, C1-4 alkyl, C1-4 haloalkyl, or C3-7 cycloalkyl;

R6 is H or selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, 3, or 4 substituents each independently
selected from the group consisting of —OH, —CN, C1-4 alkyl, C3-7 cycloalkyl, C1-4 hydroxylalkyl, —S—C1-4 alkyl, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

or R5 and R6 together with the N atom to which they are attached form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl,
each optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of halogen,
—OH, oxo, —C(?O)H, —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, —CN, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy;

R7 is selected from the group consisting of H, C1-4 alkyl, and C3-7 cycloalkyl;

R8 is selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, a 4- to 14-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, or 3 substituents each independently
selected from the group consisting of halogen, —CF3, —CN, —OH, oxo, —S—C1-4 alkyl, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

R9 is halogen, C1-4 alkyl, C1-4 haloalkyl, —CN, —SF5, —N(R5)(R6), C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkoxy, or C3-7 cycloalkyl, wherein each of the C1-4 alkyl and C3-7 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting
of halogen, —N(R5)(R6), C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

each R10 is independently selected from the group consisting of halogen, —OH, —CN, —SF5, —NO2, oxo, thiono, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, —N(R5)(R6), —N(R7)(C(?O)R8), —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR8, and —OR8, wherein each of said C1-6 alkyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl-C1-4 alkyl-, and 5- to 10-membered heteroaryl)-C1-4 alkyl- is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of
halogen, OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

or R9 and an adjacent R10 together with the two ring atoms on Q1 to which they are attached form a fused benzene ring or a fused 5- or 6-membered heteroaryl, each optionally substituted with
1, 2, 3, 4, or 5 independently selected R10a; and

each R10a is independently selected from the group consisting of halogen, —OH, —N(R5)(R6), —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, —CN, —SF5, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy,

with the proviso that when each of X1, X2, and X3 is CH2, X4 is N, and L1 is NRN, then Q1 is other than an optionally substituted piperidin-1-yl.

US Pat. No. 9,771,332

2-THIOPYRIMIDINONES

Pfizer Inc., New York, N...

1. A compound of the Formula I
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,708,405

ANTI-CXCR4 ANTIBODIES AND ANTIBODY-DRUG CONJUGATES

PFIZER INC., New York, N...

1. An isolated antibody, or an antigen binding fragment thereof, that binds to chemokine receptor 4 (CXCR4) and comprises:
a) a heavy chain variable (VH) region comprising (i) a VH CDR1 selected from the group consisting of SEQ ID NOs:107, 113 and
114; (ii) a VH CDR2 selected from the group consisting of SEQ ID NOs: 162 and 128; and (iii) a VH CDR3 set forth as SEQ ID
NO: 112; and

b) a light chain variable region (VL) region comprising (i) a VL CDR1 set forth as SEQ ID NO: 144; (ii) a VL CDR2 set forth
as SEQ ID NO: 145; and (iii) a VL CDR3 set forth as SEQ ID NO: 139.

US Pat. No. 9,518,052

PYRAZOLOPYRIDINES AND PYRAZOLOPYRIMIDINES

Pfizer Inc., New York, N...

1. A compound having the structure:

or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically
acceptable salt, wherein:

A, A? and A?? are independently C or N, where C may be unsubstituted or substituted by halo or C1-C6 alkyl;

R1 is H, cyano or halo;

R2 and R2? are independently H, C1-C6 alkyl, cyano, C1-C6 alkoxy, C1-C6 alkylthio, or C3-C8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms;

R3 is H, C1-C4 alkyl, phenyl, naphthyl, 6-membered heteroaryl or heterocyclic containing 1-3 N atoms, a 5-membered heteroaryl or heterocyclic
containing either (a) 1-4 N atoms or (b) 1 O or S atom and 0-3 N atoms, a 10-membered bicyclic heteroaryl or heterocyclic
containing 1-4 N atoms, a 9-membered bicyclic heteroaryl or heterocyclic containing either (a) 1-4 N atoms or (b) 1 O or S
atom and 0-3 N atoms, or an 8-membered bicyclic heteroaryl or heterocyclic containing (a) 1-4 N atoms or (b) 1 O or S atom
and 1-3 N atoms or (c) 2 O or S atoms and 0-2 N atoms; wherein each of said phenyl, naphthyl, heteroaryl or heterocyclic is
optionally substituted by alkyl, 1 substituent —Y—R4 and/or 1-4 substituents each independently selected from R5;

Y is a bond, —(CH2)m— or —O—;

R4 is (a) H, C1-C6 alkyl, C3-C8 cycloalkyl, halo, oxo, —OR6, —NR7R8, —SR6, —SOR9, —SO2R9, —COR6, —OCOR6, —COOR6, —NR6COR6, —CONR7R8, —NR6SO2R9, —SO2NR7R8, —NR6CONR7R8, —NR6COOR9 and —NR6SO2NR7R8; (b) phenyl or naphthyl, said phenyl and naphthyl being optionally substituted with 1-5 substituents selected from C1-C6 alkyl, C3-C8 cycloalkyl, halo, —CN, —OR6, —NR7R8, —SR6, —SOR9, —SO2R9, —COR6, —OCOR6, —COOR6, —NR6COR6, —CONR7R8, —NR6SO2R9, —SO2NR7R8, —NR6CONR7R8, —NR6COOR9 and —NR6SO2NR7R8; or (c) a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, containing 1 or 2 heteroatoms selected
from O and N, said heteroaryl being optionally substituted by 1-5 substituents selected from C1-C6 alkyl, C3-C8 cycloalkyl, halo, oxo, —OR6, —NR7R8, —SR6, —SOR9, —SO2R9, —COR6, —OCOR6, —COOR6, —NR6COR6, —CONR7R8, —NR6SO2R9, —SO2NR7R8, —NR6CONR7R8, —NR6COOR9 and —NR6SO2NR7R8;

R5 is C1-C6 alkyl, C3-C8 cycloalkyl, halo, —CN, —OR6, —NR7R8, —SR6, —SOR9, —SO2R9, —COR6, —OCOR6, —COOR6, —NR6COR6, —CONR7R8, —NR6SO2R9, —SO2NR7R8, —NR6CONR7R8, —NR6COOR9 or —NR6SO2NR7R8;

R6 is H, C1-C6 alkyl or C3-C8 cycloalkyl, said C1-C6 alkyl is optionally substituted by —NR7R8 or a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, containing 1 or 2 heteroatoms selected from
O and N, said heteroaryl being optionally substituted by 1-5 substituents selected from C1-C6 alkyl, C3-C8 cycloalkyl, halo, hydroxy and cyano;

R7 and R8 are each independently H, C1-C6 alkyl or C3-C8 cycloalkyl or are taken together with the nitrogen atom to which they are attached to form a 4-, 5- or 6-membered saturated
heterocyclic ring containing 1-2 nitrogen atoms or 1 nitrogen and 1 oxygen atom, said C1-C6 alkyl is optionally substituted by C3-C8 cycloalkyl, halo, hydroxy, amino, (C1-C6 alkyl)amino or di(C1-C6 alkyl)amino and said heterocyclic ring being optionally substituted by one or more C1-C6 alkyl or C3-C8 cycloalkyl groups;

R9 is C1-C6 alkyl or C3-C8 cycloalkyl;

R10 is —NHSO2—R?, —NR?SO2—R? or SR? where R? and R? are independently hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, phenyl, amino, C1-C6 alkylamino, di(C1-C6 alkyl)amino, heterocyclic, —(CH2)n—W?, where W? is hydroxy, C3-C8 cycloalkyl, phenyl, naphthyl, heterocyclic, 5- or 6-membered heteroaryl containing 1-3 N and/or O atoms; wherein each of said
alkyl, cycloalkyl, heterocyclic, phenyl, naphthyl or heteroaryl may be unsubstituted or substituted by phenyl, heteroaryl,
heterocyclic, halo, cyano, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, aryloxy, —SO2—R?, —NHSO2—R?, —NR?SO2—R? or SR? where R? and R? are independently phenyl, C1-C6 alkyl or C3-C8 cycloalkyl;

R11 and R12 are each independently H, hydroxy, halo, cyano, C1-C6 alkyl or C3-C8 cycloalkyl; and, m and n are independently 0, 1, 2, or 3.

US Pat. No. 10,093,655

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

Pfizer Inc., New York, N...

1. A method for treating a D1-mediated (or D1-associated) disease or disorder in a mammal, which method comprises administering to the mammal a therapeutically effective amount of a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
each of T1, T2, T3, and T4 is independently selected from the group consisting of H, halogen, —CN, —SF5, —OH, —N(Ra)(Rb), —C(?O)—N(Ra)(Rb), —C(?O)—ORc, —C(?O)—Rd, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, —S—(C1-6 alkyl), C3-7 cycloalkyl, 4- to 7-membered heterocycloalkyl, C3-7 cycloalkoxy, 5- or 6-membered heteroaryl, cyclopropylmethyl, and cyclobutylmethyl, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —S—(C1-6 alkyl), and C1-6 alkoxy is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, —OH, —CN, —N(Ra)(Rb), C1-4 alkoxy, C1-4 haloalkoxy, and —S—(C1-4 alkyl); and wherein each of the C3-7 cycloalkyl, 4- to 7-membered heterocycloalkyl, C3-7 cycloalkoxy, 5- or 6-membered heteroaryl, cyclopropylmethyl, and cyclobutylmethyl of T1, T2, and T3 is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, —OH, —CN, oxo, —N(Ra)(Rb), —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—N(Ra)(Rb), C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxylalkyl, C1-4 cyanoalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and —S—(C1-4 alkyl);
L1 is selected from the group consisting of O, S, NH, N(C1-4 alkyl), N(—C1-2 alkyl-C3-4 cycloalkyl), and N(C3-6 cycloalkyl);
each of Ra and Rb is independently selected from the group consisting of H, C1-4 alkyl, C3-7 cycloalkyl, and cyclopropylmethyl;
or Ra and Rb together with the N atom to which they are attached form 4- to 7-membered heterocycloalkyl optionally substituted with one or more substituents each independently selected from the group consisting of halogen, —OH, —CN, oxo, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—NH(C1-4 alkyl), —C(?O)—N(C1-4 alkyl)2, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxylalkyl, C1-4 cyanoalkyl, C1-4 alkoxy, —S—(C1-4 alkyl), and C1-4 haloalkoxy;
each of Rc and Rd is independently C1-4 alkyl, C3-4 cycloalkyl-C1-2 alkyl-, or C3-4 cycloalkyl;
Q1 is selected from the group consisting of Q1b, Q1c Q1d, and Q1e:

provided (a) that a ring carbon atom of the Q1 ring is attached to the benzene ring of Formula I and (b) that when L1 is NH, then the Q1 ring is substituted with at least one non-H R9, R10, R11, R12, R13, R9A, R10A, R10B, R11A, R12A, or R13A;
each of X1 and X2 is independently O or S;
each of R1, R2, R3, and R4 is independently selected from the group consisting of H, halogen, —OH, —NO2, —CN, —SF5, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, and heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CN, oxo, —OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C3-6 cycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—OR8, —C(?O)H, —C(?O)R8, —C(?O)N(R5)(R6), —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8;
or R2 and R4 together with the two carbon atoms to which they are attached form a fused 5- or 6-membered heteroaryl, a fused 5- or 6-membered heterocycloalkyl ring, a fused 5- or 6-membered cycloalkyl ring, or a fused benzene ring, wherein each of the fused rings is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, —CN, —OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, and C1-4 haloalkoxy, and wherein the fused heterocycloalkyl ring or fused cycloalkyl ring is further optionally substituted with 1, 2, or 3 oxo;
R5 is H, C1-4 alkyl, C1-4 haloalkyl, or C3-7 cycloalkyl;
R6 is H or selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of —OH, —CN, C1-4 alkyl, C3-7 cycloalkyl, C1-4 hydroxylalkyl, —S—C1-4 alkyl, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
or R5 and R6 together with the N atom to which they are attached form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl, each optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of halogen, —OH, oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)OH, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, —CN, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy;
R7 is selected from the group consisting of H, C1-4 alkyl, and C3-7 cycloalkyl;
R8 is selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CF3, —CN, —OH, oxo, —S—C1-4 alkyl, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
each R9 and R12 is independently selected from the group consisting of halogen, —OH, —CN, —SF5, —NO2, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, —N(R5)(R6), —N(R7)(C(?O)R8), —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR8, and —OR8, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl- is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)-(C1-4 alkyl), C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;
each of R10, R11 and R13 is independently selected from the group consisting of halogen, —OH, —CN, —SF5, —NO2, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, —N(R5)(R6), —N(R7)(C(?O)R8), —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR8, and —OR8, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl- is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;
each of R9A and R10A is independently selected from the group consisting of H, C1-6 alkyl, C1-6 hydroxylalkyl, C2-6 alkenyl, —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR15, —C(R14)2—OH, —C(R14)2—OS(?O)2H, —C(R14)2—OP(?O)(OH)2, —C(R14)2—OR15, —C(R14)2—OC(?O)—R15, —C(R14)2—N(R5)(R6),
each of R10B, R11A, R12A, and R13A is independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C3-7 cycloalkyl, C3-6 alkenyl, C3-6 alkynyl, C6-10 aryl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, and —C(?O)—OR8, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), —OC(?O)—C1-4 alkyl, C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;
each R14 is independently H or selected from the group consisting of C1-10 alkyl, C3-14 cycloalkyl, C2-10 alkenyl, C2-10 alkynyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-14 cycloalkyl)-C1-10 alkyl-, (4- to 14-membered heterocycloalkyl)-C1-10 alkyl-, (C6-10 aryl)-C1-10 alkyl-, (5- to 10-membered heteroaryl)-C1-10 alkyl-, wherein each of the selections of the group is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —N(R7)C(?O)R8, —N(R7)C(?O)OR8, —N(R7)S(?O)2R8, —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR8, —OR8, —S(?O)2—R8, C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —NHC(?O)H, C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;
R15 is selected from the group consisting of C1-20 alkyl, C3-14 cycloalkyl, C2-20 alkenyl, C2-20 alkynyl, C6-10 aryl, 4- to 14-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-14 cycloalkyl)-C1-20 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-20 alkyl-, (C6-10 aryl)-C1-20 alkyl-, (5- to 10-membered heteroaryl)-C1-20 alkyl-, wherein each of the selections of the group is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —N(R7)C(?O)R8, —N(R7)C(?O)OR8, —N(R7)S(?O)2R8, —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR8, —OR8, —S(?O)2—R8, C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —NHC(?O)H, C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;
t1 is 0, 1, or 2;
t2 is 0 or 1; and
t3 is 0, 1, or 2,
and wherein the D1-mediated (or D1-associated) disease or disorder is selected from the group consisting of schizophrenia, schizoaffective disorder, Parkinson's disease, and cognitive impairment.

US Pat. No. 10,071,100

THERAPEUTIC NANOPARTICLES COMPRISING A THERAPEUTIC AGENT AND METHODS OF MAKING AND USING THE SAME

Pfizer Inc., New York, N...

1. A method of treating cancer, wherein said cancer is selected from breast cancer and prostate cancer, in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a therapeutic nanoparticle; wherein said therapeutic nanoparticle comprises:a therapeutic agent selected from the group consisting of 1-(4-{[4-(dimethylamino)piperidin-1-yl]carbonyl}phenyI)-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea and pharmaceutically acceptable salt thereof;
a polymer selected from the group consisting of diblock poly(lactic) acid-poly (ethylene)glycol (PLA-PEG) copolymer, diblock poly(lactic acid-co-glycolic acid)-poly (ethylene)glycol (PLGA-PEG) copolymer, and combinations thereof; and
a substantially hydrophobic acid selected from the group consisting of dioctyl sulfosuccinic acid, 1-hydroxy-2-naphthoic acid, dodecylsulfuric acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, pamoic acid, undecanoic acid, and combinations thereof;
wherein the substantially hydrophobic acid and the therapeutic agent form a hydrophobic ion pair that is encapsulated in the therapeutic nanoparticle;
wherein the hydrophobic ion pair is dispersed throughout a polymeric matrix comprising the polymer; and
wherein PLA-PEG-GL is additionally present, wherein targeting ligand GL has the following structure:

US Pat. No. 10,040,860

THERAPEUTIC ANTIBODIES AND THEIR USES

PFIZER INC., New York, N...

1. An isolated antibody, or an antigen binding fragment thereof, which specifically binds to BCMA, wherein the antibody comprises:a VH region comprising a VH CDR1, VH CDR2, and VH CDR3 of the VH sequence shown in SEQ ID NO: 2, 3, 7, 8, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 35, 37, 39, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 83, 87, 92, 95, 97, 99, 101, 104, 106, 110, 112, 114, 118, 120, 122, 125, 127, 363, or 365; and
a VL region comprising a VL CDR1, VL CDR2, and VL CDR3 of the VL sequence shown in SEQ ID NO: 1, 4, 5, 6, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 34, 36, 38, 40, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 317, 80, 81, 82, 84, 85, 86, 88, 89, 90, 91, 93, 94, 96, 98, 100, 102, 103, 105, 107, 108, 109, 111, 113, 115, 116, 117, 119, 121, 123, 124, 126, 128, or 364.
US Pat. No. 10,023,649

METHOD OF TREATING CANCER WITH A COMBINATION OF AN ANTI-CCR4 ANTIBODY AND A 4-1BB AGONIST

Pfizer Inc., New York, N...

1. A method for treating cancer in an individual comprising administering to the individual an anti-CC chemokine receptor 4 (CCR4) antibody and a 4-1BB agonist, wherein the anti-CCR4 antibody comprises a heavy chain CDR1 comprising SEQ ID NO: 4, a heavy chain CDR2 comprising SEQ ID NO: 5, a heavy chain CDR3 comprising SEQ ID NO: 6; and a light chain CDR1 comprising SEQ ID NO: 1, a light chain CDR2 comprising SEQ ID NO: 2, a light chain CDR3 comprising SEQ ID NO: 3.

US Pat. No. 9,974,377

DUAL-ENDED LIP BALM CONTAINER

Pfizer Inc., New York, N...

1. A method for filling a lip balm mold comprising transferring a molten lip balm composition into the lip balm mold through an aperture in a partition in the lip balm mold to a fill level approaching the partition but not touching the partition;wherein said lip balm mold comprises:
a liner comprising a domed upper liner section, a lower liner section with a liner perimeter, a liner exterior, a liner interior having a lower liner interior and an upper liner interior, and a first liner engagement assembly on the lower liner interior; wherein the liner perimeter optionally has a cap engagement assembly; and
a base comprising an upper base section having a base top edge, a lower base section, a partition dividing the upper base section and the lower base section and extending to a base perimeter, the partition having a partition bottom and a partition top, with the partition top having an outer partition top section and an inner partition top section, an aperture in the partition, an upper base section exterior wall comprising a second liner engagement assembly which aligns with the first liner engagement assembly and engages the lower liner interior with the upper base section exterior wall, an upper base section interior wall, a plurality of stabilizers arising from a first area adjacent to the upper base section interior wall on the inner partition top section, rising to a level at or near horizontal with the base top edge and extending radially inward to a second area overhanging the aperture, a gap between each stabilizer and the upper base section interior wall, and a base engagement assembly on the lower base section which provides releasable engagement of a lower base section on a first lip balm mold with a lower base section on a lip balm applicator, a lip balm dispenser, or a second lip balm mold, wherein the base has three to six sides;
wherein the liner and the base are engaged through the first liner engagement assembly and the second liner engagement assembly, and
the engaged liner and base are inverted such that the partition bottom is facing upward.
US Pat. No. 9,908,850

SALT FORMS OF [R—(R*,R*)]-2-(4-FLUOROPHENYL)-?,?-DIHYDROXY-5-(1-METHYLETHYL)3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1-HEPATONIC ACID

Pfizer Inc., New York, N...

1. An atorvastatin piperazine having an x-ray powder diffraction pattern containing the following 2? peaks measured using
CuK?radiation: 7.8, 9.3, 11.8, 16.1, and 19.7.

US Pat. No. 9,872,848

STABLE FORMULATIONS FOR LYOPHILIZING THERAPEUTIC PARTICLES

Pfizer Inc., New York, N...

1. A lyophilized pharmaceutical composition comprising:
polymeric nanoparticles that comprises a poly(lactic) acid-block-poly(ethylene)glycol copolymer or poly(lactic)-co-poly(glycolic)
acid-block-poly(ethylene)glycol copolymer, and a therapeutic agent, wherein the polymeric nanoparticles have a diameter of
about 60 nm to about 140 nm;

a sugar; and
hydroxypropyl ?-cyclodextrin,
wherein upon reconstitution of the lyophilized pharmaceutical composition in an aqueous medium, the reconstituted composition
comprises 10-100 mg/mL concentration of the nanoparticles; 4 to 6 weight percent of the sugar; and 7 to 12 weight percent
of the hydroxypropyl ?-cyclodextrin, and wherein 100 mL of the reconstituted composition comprises less than 6000 microparticles
of greater than or equal to 10 microns; and less than 600 microparticles of greater than or equal to 25 microns.

US Pat. No. 9,872,913

DRUG LOADED POLYMERIC NANOPARTICLES AND METHODS OF MAKING AND USING SAME

Pfizer Inc., New York, N...

1. A method of preparing a plurality of therapeutic nanoparticles, comprising:
combining a therapeutic agent, a first polymer bound to a ligand, and a second polymer, with an organic solvent to form a
first organic phase having about 5 to about 50% solids;

combining the first organic phase with a first aqueous solution to form a second phase;
emulsifying the second phase to form an emulsion phase;
quenching the emulsion phase to form a quenched phase at least partially at a temperature of 5° C. or less;
adding a drug solubilizer to the quenched phase to form a solubilized phase of unencapsulated therapeutic agent; and
sterile filtering the solubilized phase to recover the therapeutic nanoparticles, thereby forming a slurry of therapeutic
nanoparticles having a diameter of about 80 nm to about 150 nm.

US Pat. No. 9,802,987

IMMUNOGENIC FUSION POLYPEPTIDES

Pfizer Inc., New York, N...

1. An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2.
US Pat. No. 9,744,173

2-AMINO 6-METHYL-4,4A,5,6-TETRAHYDROPYRANO[3,4-D][1,3]THIAZIN-8A(8H)-YL-1,3-THIAZOL-4-YL AMIDES

Pfizer Inc., New York, N...

1. A method of treating Alzheimer's disease in a patient, the method comprising administering to the patient a therapeutically
effective amount of a compound selected from the group consisting of
N-{2-[(4aR,6S,8aR)-2-Amino-6-methyl-4,4a,5,6-tetrahydropyrano [3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-(difluoromethoxy)pyridine-2-carboxamide;
N-{2-[(4aR,6S,8aR)-2-Amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-(difluoromethoxy)
pyrazine-2-carboxamide;

N-{2-[(4aR,6S,8aR)-2-Amino-6-methyl-4,4a, 5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-chloropyridine-2-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-fluoropyridine-2-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-(difluoromethoxy)-3-methylpyridine-2-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-(difluoromethoxy)-3-methylpyrazine-2-carboxamide;
and

N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-3-chloro-5-(difluoromethoxy)pyridine-2-carboxamide;
or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer.

US Pat. No. 9,617,275

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

Pfizer Inc., New York, N...

1. A compound of Formula I:

or an N-oxide thereof, or a pharmaceutically acceptable salt of said compound or said N-oxide, wherein:
X1 is O;

Y1 is O;

Q1 is selected from 1H-pyrazolyl, 1H-imidazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, 3-oxo-2H-pyridazinyl, 1H-2-oxo-pyrimidinyl,
1H-2-oxo-pyrazinyl, 2,4(1H,3H)-dioxo-pyrimidinyl, 1H-2-oxo-pyridinyl, isoquinolinyl, 1H-imidazo[4,5-c]pyridinyl, imidazo[1,2-a]pyridinyl,
imidazo[1,2-a]pyrimidinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, and imidazo[1,2-a]pyrazinyl, wherein each of the selections
is optionally substituted with 1, 2, 3, or 4 independently selected R7;

RT1 and RT2 are each independently selected from the group consisting of H, C1-3 alkyl, C1-3 fluoroalkyl, cyclopropyl, fluorocyclopropyl, C1-3 alkoxy, C1-3 haloalkoxy, —C(?O)—O—(C1-3 alkyl), and —C(?O)OH;

R1 is selected from the group consisting of H, F, —C(?O)OH, —C(?O)—O—(C1-3 alkyl), C1-3 alkyl, C1-3 fluoroalkyl, C3-6 cycloalkyl, and C3-6 fluorocycloalkyl, wherein said C3-6 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

R2 is selected from the group consisting of H, halogen, —CN, —OH, C(?O)OH, C(?O)—O—(C1-3 alkyl), C1-3 alkoxy, C1-3 haloalkoxy, —N(R8)(R9), C1-3 alkyl, C1-3 fluoroalkyl, C3-6 cycloalkyl, C3-6 fluorocycloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein said C3-6 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

R3 and R4 are each independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, —CN, C3-6 cycloalkyl, —C(?O)OH, C(?O)—O—(C1-4 alkyl), and halogen, wherein each of said C1-6 alkyl and C3-6 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from halo, —OH, —CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

R5 and R6 are each independently selected from the group consisting of H, halogen, —OH, —NO2, —CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, —N(R8)(R9), —N(R10)(C(?O)R11), —C(?O)—N(R8)(R9), —C(?O)—R12, —C(?O)—OR12, and —OR13, wherein each of said C1-6 alkyl, C3-7 cycloalkyl, and heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the
group consisting of halogen, —CN, —OH, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, C1-3 haloalkoxy, C3-6 cycloalkyl, —N(R14)(R15), —N(R16)(C(?O)R17), —C(?O)—OR18, —C(?O)H, —C(?O)R18, —C(?O)N(R14)(R15), and —OR19;

each R7 is independently selected from the group consisting of halogen, —OH, —CN, —NO2, oxo, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl,
heteroarylalkyl, heteroarylalkenyl, —CH?N—O—(C1-3 alkyl), —N(R14)(R15), —N(R16)(C(?O)R17), —S(?O)2N(R14)(R15), —C(?O)N(R14)(R15), —C(?O)—R12, —C(?O)—OR18, and —OR19, wherein each of said C1-6 alkyl, C3-7 cycloalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, C6-10 aryl, heterocycloalkyl and heteroaryl is optionally substituted with 1, 2, 3, or 4 substituents each independently selected
from the group consisting of halogen, OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R14)(R15), —S—(C1-3 alkyl), —S(?O)2—(C1-4 alkyl), aryloxy, arylalkyloxy optionally substituted with 1 or 2 C1-4 alkyl, oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

R8 and R9 are each independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, a 4- to 10-membered heterocycloalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl,
wherein each of said C1-6 alkyl, C3-10 cycloalkyl, 4- to 10-membered heterocycloalkyl, cycloalkylalkyl, arylalkyl, and heteroarylalkyl is optionally substituted
with 1, 2, 3, or 4 substituents each independently selected from the group consisting of —OH, —CN, C1-3 alkyl, C3-7 cycloalkyl, C1-3 hydroxylalkyl, —S—C1-3 alkyl, —C(?O)H, —C(?O)—C1-3 alkyl, —C(?O)—O—C1-3 alkyl, —C(?O)—NH2, —C(?O)—N(C1-3 alkyl)2, C1-3 haloalkyl, C1-3 alkoxy, and C1-3 haloalkoxy;

or R8 and R9 together with the N atom to which they are attached form a 4- to 10-membered heterocycloalkyl or heteroaryl optionally substituted
with 1, 2, 3, or 4 substituents each independently selected from the group consisting of halogen, —OH, oxo, —C(?O)H, —C(?O)OH,
—C(?O)—C1-3 alkyl, —C(?O)—NH2, —C(?O)—N(C1-3 alkyl)2, —CN, C1-3 alkyl, C1-3 alkoxy, C1-3 hydroxylalkyl, C1-3 haloalkyl, and C1-3 haloalkoxy;

R10 is selected from the group consisting of H, C1-3 alkyl, and C3-7 cycloalkyl;

R11 is selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, a 4- to 14-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each optionally
substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CF3, —CN, —OH, oxo, —S—C1-3 alkyl, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

R12 is H or is selected from the group consisting of C1-10 alkyl, C3-7 cycloalkyl, a 4- to 14-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each optionally
substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CF3, —CN, —OH, —C(?O)OH, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

R13 is selected from the group consisting of C1-10 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, a 4- to 14-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each optionally
substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of halogen, —N(R14)(R15), —C(?O)N(R14)(R15), —N(R16)(C(?O)R17), —C(?O)H, —C(?O)N(R16)(OR18), —C(?O)—R18, —C(?O)—OR18, —O—C(?O)R18, —CF3, —CN, —OH, —O—(C1-6 hydroxylalkyl), C1-6 alkyl, oxo, C1-6 hydroxylalkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

R14 and R15 are each independently selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, C3-10 cycloalkyl, a 4- to 14-membered heterocycloalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl,
wherein each of said C1-6 alkyl, C3-7 cycloalkyl, cycloalkylalkyl, arylalkyl, and heteroarylalkyl is optionally substituted with 1, 2, or 3 substituents each independently
selected from the group consisting of —OH, —CN, oxo, —NHC(?O)—(C1-3 alkyl), —C(?O)N(C1-3 alkyl)2, —O—(C1-6 hydroxylalkyl), —S(?O)2—C1-3 alkyl, —S—C1-3 alkyl, C1-3 alkyl, C3-7 cycloalkyl, C1-3 hydroxylalkyl, a 5- to 10-membered heteroaryl, C1-3 alkoxy, C1-3 haloalkyl, and C1-3 haloalkoxy;

or R14 and R15 together with the N atom to which they are attached form a 4- to 10-membered heterocycloalkyl or 5- to 10-membered heteroaryl
optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, oxo,
—OH, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, C1-3 haloalkoxy, C1-3 hydroxylalkyl, C2-4 alkoxyalkyl, oxo, a 5- to 6-membered heteroaryl, —NH2, —N(C1-3 alkyl)2, —S(?O)2—C1-3 alkyl, —S—C1-3 alkyl, —C(?O)H, —C(?O)OH, —C(?O)NH2, and —C(?O)—C1-3 alkyl;

R16 is selected from the group consisting of H, C1-3 alkyl, and C3-7 cycloalkyl;

R17 is selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, a 4- to 14-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each optionally
substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CF3, —CN, —OH, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

R18 is H or is selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, a 4- to 14-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each optionally
substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CF3, —CN, —OH, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

R19 is selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, a 4- to 14-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each optionally
substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —N(R14)(R15), —C(?O)N(R14)(R15), —N(R18)(C(?O)R17), —C(?O)—R18, —C(?O)—OR18, —CF3, —CN, —OH, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy; and

RN is selected from the group consisting of H, C1-6 alkyl, C3-6 cycloalkyl, C3-6 fluorocycloalkyl, heteroarylalkyl, and arylalkyl, wherein each of said C3-6 cycloalkyl, heteroarylalkyl, and arylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently
selected from halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy.

US Pat. No. 9,593,097

AXL INHIBITORS

Pfizer Inc., New York, N...

1. A compound of formula (I):

wherein:
each X is N or CR6, where at least one X is N, where each R6 is independently selected from the group consisting of hydrogen, halogen, (C1-C8)alkyl, (C2-C8)alkenyl, (C1-C8)alkynyl, (C1-C8)haloalkyl, —(C1-C4)alkylene-R7, —OR7, —CN, —NO2 and —NR7R7, where each R7 is independently selected from the group consisting of hydrogen and (C1-C8)alkyl, and where each said (C1-C8)alkyl in R6 is optionally substituted by one or more substituents independently selected from the group consisting of halogen, hydroxyl
and (C1-C8)alkoxy;

Y is Y1-Y2 or Y2-Y1, where Y1 is absent or is selected from the group consisting of (C1-C8)alkylene, (C2-C8)alkenylene, (C1-C8)haloalkylene, (C1-C8)heteroalkylene, and (C2-C8)heteroalkenylene, and where Y1 is optionally substituted with one or more R8 where each R8 is independently selected from the group consisting of halogen, (C1-C10)alkyl, —CN, ?O, —R9—OR9, —SR9 and —NO2, and where each R9 is independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl, (C6-C12)aryl and 5-12 membered heteroaryl, and where Y2 is absent or oxygen;

Z is Z1-Z2, where each of Z1 and Z2 is independently absent or selected from the group consisting of (C1-C8)alkylene, (C2-C8)alkenylene, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl and (C1-C8)heteroalkylene, where Z is optionally independently substituted with one or more R10 where each R10 is independently selected from the group consisting of halogen, (C1-C8)alkyl, —CN, ?O, —OR11 and —NO2, and where each R11 is independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl, (C6-C12)aryl and 5-12 membered heteroaryl;

each R1 is independently selected from the group consisting of hydrogen, halogen, (C1-C8)alkyl, (C1-C8)haloalkyl, —(C1-C4alkyl)R7, —OR7, —CN, —C(O)R7, —CO2R7, —C(O)NR7R7, —SR7, —SOR7, —SO2R7, —SO2NR7R7, —NO2, —NR7R7, —NR7C(O)R7, —NR7C(O)NR7R7, —NR7C(O)OR7, —NR7SO2R7, —NR7SO2NR7R7, —OC(O)R7 and —OC(O)NR7R7; where any set of two R1 on the same or different piperidine carbons optionally join to form a spirocyclic, fused or bridged ring system comprising
1-4 non-piperadine members and 1-2 heteroatoms selected from N, O and S, and where any set of two R1 on adjacent piperidine carbons optionally join to form a carbon-carbon bond;

R2 and R3 are each independently selected from the group consisting of hydrogen, halogen, (C1-C8)alkyl, (C1-C8)haloalkyl, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl, —OR13, —NR14R14, —C(O)NR14R14, —SO2NR14R14, —NR14SO2R14, —SO2R14, (C6-C12)aryl and 5-12 membered heteroaryl, where each R13 is independently selected from the group consisting of hydrogen, (C1-C4)alkyl, (C1-C4)haloalkyl, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl, (C6-C12)aryl and 5-12 membered heteroaryl, where each R14 is independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl, (C6-C12)aryl and 5-12 membered heteroaryl, or two R14 together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl, each
optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S, and where R2, R3 or both R2 and R3 is optionally substituted with one or more substituents independently selected from halogen, (C1-C8)alkyl, hydroxyl, (C1-C4)alkoxy, —CN, NH2, NH(C1-C4alkyl), N(C1-C4alkyl)2, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl, (C6-C12)aryl and 5-12 membered heteroaryl;

or R2 and R3 join to form a heterocyclic ring selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, piperadinonyl, piperazinonyl
and morpholinyl, optionally substituted with one or more substituents independently selected from the group consisting of
R15 and (C1-C4)alkylene-R15, where R15 is independently selected from the group consisting of halogen, (C1-C4)alkyl, (C1-C4)haloalkyl, hydroxyl, (C1-C4)alkoxy, CN, NH2, NH(C1-C4alkyl), N(C1-C4alkyl)2, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl, (C6-C12)aryl and 5-12 membered heteroaryl;

R4 is selected from the group consisting of (C1-C8)alkyl, (C1-C8)haloalkyl, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl and —C(O)NR14R14, where R4 is optionally substituted with one or more R12 independently selected from halogen, hydroxyl, (C1-C4)alkoxy, —CN, NH2, NH(C1-C4alkyl), N(C1-C4alkyl)2, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl, (C6-C12)aryl and 5-12 membered heteroaryl, and where, when R12 is (C1-C4)alkoxy, NH(C1-C4alkyl), N(C1-C4alkyl)2, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl, (C6-C12)aryl or 5-12 membered heteroaryl, it is optionally substituted by one or more substituents independently selected from halogen,
hydroxyl, (C1-C4)alkoxy, —CN, NH2, NH(C1-C4alkyl), N(C1-C4alkyl)2, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl, (C6-C12)aryl and 5-12 membered heteroaryl;

R5 is a mono- or bi-cyclic aryl or a mono- or bi-cyclic heteroaryl, optionally substituted with one or more substituents independently
selected from the group consisting of (C1-C8)alkyl, halogen, (C1-C8)haloalkyl, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl, —OR13, —NR14R14, —C(O)NR14R14, —SO2NR14R14, —SO2R14, —NR14SO2R14, CN, mono- or bi-cyclic aryl and mono- or bi-cyclic heteroaryl, said one or more optional substituents being further optionally
substituted with one or more substituents selected from the group consisting of (C1-C8)alkyl, (C1-C8)alkylene-OH, (C1-C8)haloalkyl, (C3-C10)cycloalkyl, 3-12 membered heterocyclyl, —OR13, —NR14R14, —C(O)NR14R14, —SO2NR14R14, —SO2R14, —NR14SO2R14 and CN;

and m is 1-9,
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,561,269

NEISSERIA MENINGITIDIS COMPOSITIONS AND METHODS THEREOF

Pfizer Inc., New York, N...

1. An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 76.

US Pat. No. 9,504,669

SPLICEOSTATIN ANALOGS AND METHODS FOR THEIR PREPARATION

Pfizer Inc., New York, N...

1. A method for treating cancer comprising administering to a patient an amount of a compound of formula (I):

wherein:
a dashed line represents an optional bond;
each X1 is independently selected from the group consisting of: —O—, —S— and —NR—;

each X2 is independently selected from the group consisting of: —O—, —S— and —NR—;

R1 is selected from the group consisting of: —R, —OR, —OCOR13, —OCONR14R15, —OCON(R14)NR(R15), ?O (double bond to oxygen) and —NR14R15;

R2 and R3 are independently selected from the group consisting of: hydrogen and C1-6alkyl;

R4 and R5 are independently selected from the group consisting of: hydrogen, —OR, —NR14R15 and oxo;

R6 and R7 are independently selected from the group consisting of: hydrogen, halogen, hydroxyl and C1-6alkyl optionally substituted with 1-3 substituents independently selected from hydroxyl and halogen,

R6 and R7, together with the carbon atom to which they are bound, form a C2-5alkylidene optionally substituted with 1-3 substituents independently selected from R,

R6 and R7 together are oxo, or

R6 and R7, together with the carbon atom to which they are bound, form a 3- to 5-membered heterocycloalkyl moiety comprising 1 or 2
heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, wherein said heterocycloalkyl
moiety may be optionally substituted with one to three substituents independently selected from R;

R8 is hydrogen, C1-6alkyl or —OR;

R9 is independently selected from —(C(R)2)m—C(O)OR, —(C(R)2)m—C(O)NR14R15, —(C(R)2)m—NR14R15, —(C(R)2)m—N(R)COR13, —(C(R)2)m—C(O)—SR, —(C(R)2)m—C(O)NR14N(R)R15, —(C(R)2)m—NR—C(O)—NR14R15 and (C(R)2)m—NR14N(R)R15;

R13 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8carbocyclyl, C3-8heterocyclyl, C1-6alkyl-C6-14aryl, C1-6alkyl-O5-14heteroaryl, wherein R13 is optionally substituted with —NRR or —SO2NRR;

each R14 and R15 is independently selected from the group consisting of: hydrogen, hydroxyl, —NRR, —NRNR2, —C3-10carbocyclyl, —C1-6alkylene-C3-10carbocyclyl, —C3-10heterocyclyl, —C1-6alkylene-C3-10heterocyclyl, —(CH2CH2O)1-6CH2CH2C(O)OR, —(CH2CH2O)1-6CH2CH2NRR, —C1-6alkyl, C6-14aryl, —C1-6alkylene-C6-14aryl and —C5-14heteroaryl;

or R14 and R15, together with the atom or atoms to which they are joined, form a C3-10heterocyclyl ring,

wherein R14, R15, or both, or a ring formed with R14 and R15, are optionally substituted with —(C(R)2)m—R18 where each R18 is independently selected from (i) —NRR, (ii) —C(NRR)(C(O)OR), (iii) —S—R, (iv) aryl or heteroaryl optionally substituted
with one or more of halogen, —CF3, —(C(R)2)m—NRR or —(C(R)2)m—SO2NRR, (v) —SO2R, (vi) —S—S—C1-6alkyl-C(O)OR, (vii) —SO2NRR, (viii) —C(O)NRR, (ix) —C(O)OR, (x) —C4-6 cycloalkyl optionally substituted with —NRR, —SO2NRR or —NR—C(O)(CH2)0-6NRR, (xi) —R, (xii) —OR, (xiii) —N(R)NRR, (xiv) —C(O)N(R)NRR, —(C(R)2)m—O—NRR and —S—S—C1-6alkyl-NRR;

each R is independently selected from the group consisting of: hydrogen and —C1-6alky; and

each m is independently 0, 1, 2 or 3;
or a pharmaceutically acceptable salt thereof, said amount being effective to that cancer.
US Pat. No. 10,016,362

APIXABAN LIQUID FORMULATIONS

BRISTOL-MYERS SQUIBB COMP...

1. A liquid formulation comprising apixaban and a vehicle,wherein:
water content of the vehicle is about 20% to about 30% w/w of the vehicle;
non-ionic surfactant content of the vehicle is about 11% to about 14% w/w of the vehicle;
hydrophilic polymer content of the vehicle is about 1% to about 7% w/w of the vehicle;
polyhydric alcohol content of the vehicle is about 31% to about 54% w/w of the vehicle;
polyethylene glycol content of the vehicle is about 4% to about 6% w/w of the vehicle;
carbohydrate content of the vehicle is 0% to about 25% w/w of the vehicle,
wherein the vehicle comprises at least one ionic surfactant such that ionic surfactant content of the vehicle is up to about 2% w/w of the vehicle, and
wherein a solubility of apixaban in the vehicle is at least 0.50 mg/mL.

US Pat. No. 9,932,307

PROCESS FOR ANNEALING AMORPHOUS ATORVASTATIN

Pfizer Inc., New York, N...

1. A process for annealing amorphous atorvastatin comprising irradiating amorphous atorvastatin with microwave at a frequency ranging from about 1 GHz to about 100 GHz and power of about 1 watt to about 3000 watts either in a continuous or pulse mode for a time period ranging from about 1 second to about 10 hours.
US Pat. No. 9,920,054

METHYL- AND TRIFLUOROMETHYL-SUBSTITUTED PYRROLOPYRIDINE MODULATORS OF RORC2 AND METHODS OF USE THEREOF

Pfizer Inc., New York, N...

1. (R)-3-Cyano-N-(3-(1-(cyclopentanecarbonyl)-2,2 dimethylpiperidin-4-yl)-1,4-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,872,922

ANTI-EFNA4 ANTIBODY-DRUG CONJUGATES

Pfizer Inc., New York, N...

1. A method of treating an EFNA-associated neoplastic disorder comprising administering a therapeutically effective amount
of a composition comprising an antibody-drug conjugate of the formula Ab-(L-D) to a subject in need thereof, wherein:
(a) Ab is an antibody, or antigen-binding fragment thereof, that binds to EFNA4 and comprises a heavy chain variable region
comprising three CDRs set forth as SEQ ID NOs: 15, 19, and 23 and a light chain variable region comprising three CDRs set
forth as SEQ ID NOs: 29, 33, and 35; and

(b) L-D is a linker-drug moiety, wherein L is a linker and D is a drug, and wherein D is a calicheamicin or calicheamicin
derivative.

US Pat. No. 9,835,572

THERAPEUTIC POLYMERIC NANOPARTICLE COMPOSITIONS WITH HIGH GLASS TRANSITION TEMPERATURE OR HIGH MOLECULAR WEIGHT COPOLYMERS

PFIZER INC., New York, N...

1. A method for identifying therapeutic polymeric nanoparticle compositions with a desired therapeutic agent release rate
profile, comprising:
a) providing a first aqueous suspension of at least one first plurality of polymeric nanoparticles each comprising a therapeutic
agent, a block copolymer having at least one hydrophobic portion and at least one hydrophilic portion, wherein the therapeutic
agent is selected from the group consisting of taxane agents, vinca alkaloids, nitrogen mustard agents, mTOR inhibitors, boronate
esters; and peptide boronic acid compounds;

b) determining the nanoparticle glass transition temperature for the first aqueous suspension;
c) varying the amount or molecular weight of the hydrophobic portion of the block copolymer to provide a second aqueous suspension
comprising a plurality of polymeric nanoparticles each comprising the therapeutic agent, if the glass transition temperature
of step b) is below 37° C.; and

d) repeating steps b) and c) until an aqueous suspension with a glass transition temperature of between about 37° C. and about
50° C. and the desired therapeutic agent release rate profile is obtained.

US Pat. No. 9,822,150

NEISSERIA MENINGITIDIS COMPOSITIONS AND METHODS THEREOF

Pfizer Inc., New York, N...

1. A method of inducing a bactericidal immune response against a Neisseria meningitidis serogroup B subfamily A strain and against a Neisseria meningitidis serogroup B subfamily B strain in a human, comprising administering to the human an effective amount of a composition, said
composition comprising
a) a first lipidated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1, and
b) a second lipidated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2.

US Pat. No. 9,815,832

AZABENZIMIDAZOLE COMPOUNDS

Pfizer Inc., New York, N...

1. A method of treating a patient suffering from a disease or condition mediated by the PDE4B isoform, wherein said disease
or condition is selected from the group consisting of schizophrenia, cognitive deficits associated with Alzheimer's disease,
major depressive disorder (MDD), multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, osteoarthritis,
irritable bowel disease, alopecia, dermatitis, eczema, atopic dermatitis, ulcerative colitis, Crohn's disease, oral ulcers
associated with Behçet's disease, ankylosing spondylitis, multiple sclerosis, asthma, obstructive or inflammatory airway disease,
and allergic rhinitis, the method comprising administering to said patient in need of said treatment a therapeutically effective
amount of a compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is represented by a substituent selected from the group consisting of (C3-C10)cycloalkyl, a (4- to 10-membered)heterocycloalkyl, (C6-C10)aryl, and a (5- to 10-membered) heteroaryl; wherein said (C3-C10)cycloalkyl, (C6-C10)aryl and (5- to 10-membered)heteroaryl are substituted with (R2)b; and said (4- to 10-membered)heterocycloalkyl is optionally substituted at one to five carbon atoms with a substituent independently
selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy, and cyano, and optionally substituted at each available nitrogen with (C1-C6)alkyl;

R2 is represented by a substituent independently selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio; —C(O)NR4R5, hydroxy, and cyano;

R3, if present, at each occurrence is represented by a substituent independently selected from the group consisting of halogen,
(C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy, and cyano;

R4 and R5 are each represented by a substituent independently selected from the group consisting of hydrogen, (C1-C6)alkyl, and (C3-C6)cycloalkyl;

one of R6 and R7 is represented by a substituent selected from the group consisting of hydrogen, (C1-C6)alkyl, —(CH2)m—(C3-C10)cycloalkyl, —(CH2)m-(4- to 10-membered)-heterocycloalkyl, —(CH2)m—(C6-C10)aryl, and —(CH2)m-(5- to 10-membered)heteroaryl and the other is represented by a substituent selected from the group consisting of (C1-C6)alkyl, —(CH2)m—(C3-C10)cycloalkyl, —(CH2)m-(4- to 10-membered)-heterocycloalkyl, —(CH2)m—(C6-C10)aryl, and —(CH2)m-(5- to 10-membered)heteroaryl; wherein:

i) said R6 and R7 (C1-C6)alkyl substituent is optionally substituted with one to five substituents independently selected from the group consisting
of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, and cyano;

ii) said R6 and R7 (C3-C10)cycloalkyl substituent is optionally substituted with one to five substituents independently selected from the group consisting
of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy and cyano;

iii) said R6 and R7 (C6-C10)aryl substituent is optionally substituted with one to five substituents independently selected from the group consisting
of halogen, (C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy and cyano;

iv) said R6 and R7 (5- to 10-membered)heteroaryl substituent is optionally substituted with one to five substituents independently selected from
the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy, and cyano; and

v) said R6 and R7 (4- to 10-membered)heterocycloalkyl substituent is optionally substituted at one to five carbon atoms with a substituent independently
selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy, and cyano, and optionally substituted at each available nitrogen with (C1-C6)alkyl; or R6 and R7 taken together with the nitrogen to which they are attached form a (4- to 10-membered)heterocycloalkyl, wherein said (4- to
10-membered) heterocycloalkyl is optionally substituted at one to five carbon atoms with a substituent independently selected
from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —C(O)NR4R5, hydroxy, and cyano;

a is represented by an integer selected from 0, 1, 2 or 3;
b is represented by an integer selected from 0, 1, 2, 3, 4 or 5; and
m is represented by an integer selected from 0, 1, 2 or 3.

US Pat. No. 9,789,110

DIACYLGLYCEROL ACYLTRANSFERASE 2 INHIBITORS

Pfizer Inc., New York, N...

1. A method for treating non-alcoholic steatohepatitis (NASH) in humans comprising the step of administering to a human in
need of such treatment a therapeutically effective amount of a compound having the structure:

or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,758,538

PYRIMIDINE DERIVATIVES

PFIZER INC., New York, N...

1. A compound of formula (I)
or a pharmaceutically acceptable salt thereof,wherein
X is N or CR2;

R1 is hydrogen or methyl;

R2 is hydrogen, fluorine, or chlorine;

R3 is methyl or NH2;

Y is N or CR4;

R4 is hydrogen, cyano, or fluorine;

R5 is hydrogen, methyl, or CF3;

Z is NR6 or O;

R6 is hydrogen or C1-C3 alkyl;

R7 is hydrogen,

C1-C4 alkyl, optionally substituted by one, two, or three substituents selected from the group consisting of fluorine, hydroxy,
and NH2,

—CH2—(C3-C4 cycloalkyl),

—C(O)—(C1-C6 alkyl), optionally substituted by one, two, or three substituents selected from the group consisting of fluorine, NH2, hydroxy, methoxy, and phenyl,

—C(O)—(C3-C4 cycloalkyl), optionally substituted by one or two substituents selected from the group consisting of fluorine and C1-C4 alkyl,

—[(CH2)]p—C(O)-(4-5 membered heterocycloalkyl), optionally substituted by one or two substituents selected from the group consisting
of fluorine and C1-C4 alkyl,

—C(O)-(5-6 membered heteroaryl), optionally substituted by one or two substituents selected from the group consisting of fluorine
and C1-C4 alkyl,

—[(CH2)]p—C(O)—[N(R10)(R11)],

—C(O)O—(C1-C4 alkyl), optionally substituted by one, two, or three substituents selected from the group consisting of fluorine, NH2, hydroxy, methoxy, and phenyl,

—C(O)O—(C3-C4 cycloalkyl), optionally substituted by one or two substituents selected from the group consisting of fluorine and C1-C4 alkyl,

—S(O)2—(C1-C4 alkyl),

4-6 membered heterocycloalkyl, optionally substituted by one or two substituents selected from the group consisting of oxo
and C1-C4 alkyl, or

5-6 membered heteroaryl, optionally substituted by one or two substituents selected from the group consisting of oxo and C1-C4 alkyl;

R8 is —CH2OH or —CH2—O—P(O)(OH)2;

R9 is fluorine or methyl;

R10 is hydrogen or methyl;

R11 is C1-C4 alkyl, optionally substituted by one, two, or three fluorine atoms,

provided that R10 and R11 may form a 4-6 membered heterocycloalkyl ring, when p is 0;

m is 0, 1, or 2;
n is 0, 1, or 2; and
p is 0 or 1.
US Pat. No. 9,750,756

CELECOXIB COMPOSITIONS

Pfizer Inc., New York, N...

1. A pharmaceutical composition comprising one or more orally deliverable dose units, each comprising particulate celecoxib
in an amount of about 10 mg to about 1000 mg in intimate mixture with one or more pharmaceutically acceptable excipients,
and having a distribution of celecoxib particle sizes such that D90 of the particles is less than 200 um; said composition exhibiting upon oral administration a relative bioavailability not
less than about 50% by comparison with an orally delivered solution containing celecoxib at the same dosage rate, wherein
said excipients include:
a. one or more pharmaceutically acceptable diluents in a total amount of about 5% to about 99% by weight of the composition;
b. one or more pharmaceutically acceptable disintegrants in a total amount of about 0.2% to about 30% by weight of the composition;
c. one or more pharmaceutically acceptable binding agents in a total amount of about 0.5% to about 25% by weight of the composition;
d. one or more pharmaceutically acceptable wetting agents in a total amount of about 0.25% to about 15% by weight of the composition;
and

e. one or more pharmaceutically acceptable lubricants in a total amount of about 0.1% to about 10% by weight of the composition.
US Pat. No. 9,751,877

SUBSTITUTED PYRIDO[1,2-A]PYRAZINES FOR THE TREATMENT OF NEURODEGENERATIVE AND NEUROLOGICAL DISORDERS

PFIZER INC., New York, N...

1. The compound 2-[(1S)-1-{(2S,5R)-5-[4-chloro-5-fluoro-2-(trifluoromethyl)phenyl]tetrahydrofuran-2-yl}ethyl]-7-(4-methyl-1H-imidazol-1-yl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione.

US Pat. No. 9,751,895

N-[2-(2-AMINO-6,6-DISUBSTITUTED-4,4A,5,6-TETRAHYDROPYRANO[3,4-D][1,3]THIAZIN-8A(8H)-YL)-1,3-THIAZOL-4-YL]AMIDES

Pfizer Inc., New York, N...

1. The compound of of Formula la

or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer;
wherein
R1 is a C5-9bicycloalkyl; and

R2 and R3 are each independently selected from C1-6alkyl or C3-7cycloalkyl; wherein the C1-6alkyl is optionally substituted with one to three fluoro or C1-3alkoxy; or R2 and R3 taken together with the carbon to which they are attached form a C3-6cycloalkyl ring or a 4-to 6-membered heterocycloalkyl ring, each of which is optionally and independently substituted with
one to three fluoro, C1-3alkyl or C1-3alkoxy.

US Pat. No. 9,637,500

SOLID FORMS OF A MACROCYCLIC KINASE INHIBITOR

Pfizer Inc., New York, N...

1. A crystalline acetic acid solvate of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiaza-cyclotetradecine-3-carbonitrile,
having a powder X-ray diffraction pattern comprising a peak at a 2? value of: 12.9° 2?±0.2° 2?.

US Pat. No. 9,670,201

METHYL- AND TRIFLUOROMETHYL-SUBSTITUTED PYRROLOPYRIDINE MODULATORS OF RORC2 AND METHODS OF USE THEREOF

Pfizer Inc., New York, N...

1. A compound of Formula I:

or a pharmaceutically acceptable salt, pharmaceutically active metabolite, pharmaceutically acceptable prodrug, or pharmaceutically
acceptable solvate thereof, wherein,

Y is —CF3;

X is phenyl optionally substituted with one, two, three, four or five substituents independently selected from the group consisting
of —CH3, —CH2CH3, —CH2OH, —OH,

—OCH3, —SCH3, —OCH2CH3, —OCH2CH3, —OCH2CH2OH, —OCH2CH2OCH3, —F, —Cl, —Br and —CN;

R1 is —CH3 or —CH2CH3;

W is
each optionally substituted with one, two, three, four or five —CH3; and
R2 is (C1-C6)alkyl, (C3-C10)cycloalkyl, phenyl, tetrahydrothiophenyl, thietanyl or indanyl, optionally substituted with one, two, three, four or five
substituents independently selected for each occurrence from the group consisting of —F, —Cl, —Br, —OH, (C1-C3)alkyl, (C1-C3)haloalkyl and (C3-C10)cycloalkyl.

US Pat. No. 9,605,007

2-AMINO-6-METHYL-4,4A,5,6-TETRAHYDROPYRANO[3,4-D][1,3]THIAZIN-8A(8H)-YL-1,3-THIAZOL-4-YL AMIDES

Pfizer Inc., New York, N...

1. A compound selected from the group consisting of:
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1-(difluoromethyl)-1H-pyrazole-3-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-4-chloro-1-(difluoromethyl)-1H-pyrazole-3-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1-methyl-1H-pyrazole-3-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1,3-dimethyl-1H-pyrazole-4-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-3-cyclobutyl-1-methyl-1H-pyrazole-5-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1,3-dimethyl-1H-pyrazole-5-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}1-methyl-1H-pyrazole-4-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1-methyl-5-(2-methylpropyl)-1H-pyrazole-3-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1-methyl-3-(propan-2-yl)-1H-pyrazole-5-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1-ethyl-1H-pyrazole-4-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1,5-dimethyl-1H-pyrazole-3-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1-cyclopropyl-1H-pyrazole-4-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-chloro-1-methyl-1H-pyrazole-3-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1-(difluoromethyl)-1H-pyrazole-4-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1-cyclopropyl-1H-pyrazole-3-carboxamide;
N-{2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-1-cyclopropyl-1H-pyrazole-5-carboxamide;
or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer.

US Pat. No. 9,598,421

IMIDAZOPYRIDAZINE COMPOUNDS

Pfizer Inc., New York, N...

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of —(CH2)m—(C3-C8)cycloalkyl, —(CH2)m-(4- to 10-membered)heterocycloalkyl, —(CH2)m—(C6-C10)aryl and —(CH2)m-(5- to 14-membered)heteroaryl, and, where chemically permissible, the (C3-C8)cycloalkyl, (4- to 10-membered)heterocycloalkyl, (C6-C10)aryl and (5- to 14-membered)heteroaryl moieties are optionally substituted with one to five R2;

when present, each R2 is independently selected from the group consisting of halogen, oxo, cyano, hydroxy, —SF5, nitro, optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, optionally substituted (C1-C6)alkylthio, optionally substituted (C1-C6)alkoxy, —N(R4)(R5), —N(R4)(C?(O)R5), —C(?O)N(R4)(R5), —C(?O)—O—N(R4)(R5), —C(?O)—R4, —C(?O)—OR4, and optionally substituted (C3-C8)cycloalkyl;

when present, each R3 is independently selected from the group consisting of halogen, cyano, hydroxy, —SF5, nitro, optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, optionally substituted (C1-C6)alkylthio, optionally substituted (C1-C6)alkoxy, —N(R4)(R5), —N(R4)(C?(O)R5), —C(?O)N(R4)(R5), —C(?O)—O—N(R4)(R5), —C(?O)—R4, and —C(?O)—OR4;

R4 and R5 are each independently selected from the group consisting of hydrogen and optionally substituted (C1-C6)alkyl;

R6 and R7 are each independently selected from the group consisting of hydrogen, optionally substituted (C1-C6)alkyl, —(CH2)n—(C3-C8)cycloalkyl, —(CH2)n-(4- to 10-membered) heterocycloalkyl, —(CH2)n—(C6-C10)aryl, and —(CH2)n-(5- to 10-membered)heteroaryl, and where chemically permissible, the (C3-C8)cycloalkyl, (4- to 10-membered)heterocycloalkyl, (C6-C10)aryl, and (5- to 10-membered)heteroaryl are optionally substituted with one to five R8; or

R6 and R7 taken together with the nitrogen to which they are attached form a (4- to 10-membered)heterocycloalkyl, and where chemically
permissible, the (4- to 10-membered)-heterocycloalkyl is optionally substituted with one to five R9;

when present, each R8 is independently selected from the group consisting of halogen, oxo, cyano, hydroxy, —SF5, nitro, optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, optionally substituted (C1-C6)alkylthio, optionally substituted (C1-C6)alkoxy, —N(R4)(R5), —N(R4)(C?(O)R5), —C(?O)N(R4)(R5), —C(?O)—O—N(R4)(R5), —C(?O)—R4, and —C(?O)—OR4;

when present, each R9 is independently selected from the group consisting of halogen, oxo, cyano, hydroxy, —SF5, nitro, optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, optionally substituted (C1-C6)alkylthio, optionally substituted (C1-C6)alkoxy, —N(R4)(R5), —N(R4)(C?(O)R5), —C(?O)N(R4)(R5), —C(?O)—O—N(R4)(R5), —C(?O)—R4, and —C(?O)—OR4;

b is represented by an integer selected from 0, 1, 2, or 3;
m is represented by an integer selected from 0, 1, or 2; and
n is represented by an integer selected from 0, 1, 2, 3 or 4.

US Pat. No. 10,137,088

THERAPEUTIC NANOPARTICLES HAVING EGFR LIGANDS AND METHODS OF MAKING AND USING SAME

Pfizer Inc., New York, N...

1. A therapeutic nanoparticle, comprising:about 0.2 to about 35 weight percent of a therapeutic agent; and
about 50 to about 98 weight percent of a diblock poly(lactic)acid-poly(ethylene)glycol copolymer or a diblock poly(lactic)-co-poly(glycolic)acid-poly(ethylene)glycol copolymer; and
about 2% to about 12% PLA-PEG-EGFR ligand density, wherein the EGFR ligand is bound or associated to an azide functionalized PEG-PLA, wherein PLA is poly(lactic)acid and PEG is poly(ethylene)glycol; and wherein the EGFR ligand is a peptidyl ligand comprising a sequence selected from the group consisting of: Ac-DPCTWEVWGRECLQGGK(PEG4-DBCO)-CONH2 (SEQ ID NO: 185), Ac-DACTWEVWGRECLQGGK(PEG4-DBCO)-CONH2 (SEQ ID NO: 186), Ac-DPCT(2Ind)GEV(5MeO)WGRECLQGGK(PEG4-DBCO)-CONH2(SEQ ID NO: 187), Ac-DPPenTWEVWGREPenLQGGK(PEG4-DBCO)-CONH2 (SEQ ID NO: 188), AcDAPenTWEVWGREPenLQGGK(DBCO)-CONH2 (SEQ ID NO: 189), Ac-DACT(2Ind)GEV(5MeO)WGRECLQGGK(DBCO)-CONH2 (SEQ ID NO: 190), Ac-DPPenT(2Ind)GEV(5MeO)WGREPenLQGGK(DBCO)-CONH2 (SEQ ID NO: 191), Ac-DAPenT(2Ind)GEV(5MeO)WGREPenLQGGK(DBCO)-CONH2 (SEQ ID NO: 192), Ac-DAPenTWEVWGREPenLQGGK(DBCO)-CONH2 (SEQ ID NO: 193), Ac-DPCTWEVWGRECLQGGK(PEGS-DBCO)-CONH2 (SEQ ID NO: 194), Ac-DACT (2Ind)GEV(5MeO)WGRECLQGGK(DBCO)-CONH2 (SEQ ID NO: 195), AcDPPenT(2Ind)GEV(5MeO)WGREPenLQGGK(DBCO)-CONH2 (SEQ ID NO: 196), and AcDAPenT(2Ind)GEV(5MeO)WGREPenLQGGK(DBCO)-CONH2 (SEQ ID NO: 197), Ac-DPCTWEVWGRECLQGGK(PEG5-DBCO)-CONH2 (SEQ ID NO: 198), or modifications thereof.

US Pat. No. 10,125,130

CYCLOALKYL-LINKED DIHETEROCYCLE DERIVATIVES

Pfizer Inc., New York, N...

1. A compound of formula (IVa)whereinL is -(C4-C10 cycloalkyl)- optionally substituted by one to three substituents selected from the group consisting of halogen, cyano, C1-C4 alkyl, hydroxy, and C1-C4 alkoxy;
R1 is hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, —C(O)R10a, or 5-6 membered heteroaryl, wherein the C3-C6 cycloalkyl and the 5-6 membered heteroaryl are independently optionally substituted by one or two R15 groups;
R2 is hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, —C(O)R10b, or 5-6 membered heteroaryl, wherein the C3-C6 cycloalkyl and the 5-6 membered heteroaryl are independently optionally substituted by one or two R15 groups;
R3 and R4 are each independently hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy or C3-C6 cycloalkyl;
R7 and R8 are each independently hydrogen, halogen, cyano, C1-C2 alkyl, hydroxy, C1-C2 alkoxy, or —N(R11)(R12), wherein the C1-C2 alkyl and the C1-C2 alkoxy are each independently optionally substituted by halogen or hydroxy;
R10a and R10b are each independently hydrogen, C1-C4 alkyl, —[C(R13)(R14)]z-(C4-C10 cycloalkyl), —[C(R13)(R14)]z-(4-6 membered heterocycloalkyl), —[C(R13)(R14)]z-(C6-C10 aryl), or —[C(R13)(R14)]z-(5-10 membered heteroaryl), wherein the C1-C4 alkyl, the C4-C10 cycloalkyl, the 4-6 membered heterocycloalkyl, the C6-C10 aryl, and the 5-10 membered heteroaryl in R10a and R10b are each independently optionally substituted by one, two or three halogen, cyano, C1-C6 alkyl, hydroxy, C1-C6 alkoxy, —(CH2)w—N(R11)(R12), —(CH2)w—C(O)N(R11)(R12), —C(O)OR11, —N(R11)C(O)R12, —S(O)2R11, or —S(O)N(R11)(R12) groups;
each R11, R12, R13, R14 and R15 is independently hydrogen, C1-C4 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, or 3-6 membered heterocycloalkyl, wherein the C1-C4 alkyl, the C3-C6 cycloalkyl, and the 3-6 membered heterocycloalkyl are each independently optionally substituted by one, two or three substituents selected from the group consisting of halogen, cyano, hydroxy, and methoxy;
w is 0, 1, 2 or 3;
x is 1;
and
z is 0, 1, 2 or 3;
or a pharmaceutically acceptable salt thereof.

US Pat. No. 10,039,778

SUBSTITUTED-6,8-DIOXABICYCLO[3.2.1]OCTANE-2,3-DIOL COMPOUNDS AS TARGETING AGENTS OF ASGPR

Pfizer Inc., New York, N...

1. A compound of Formula (A)
wherein
R1 is —Z—X—Y wherein X is a linker of any of structures L1-L10

each Q is independently absent or is C(O), C(O)—NR4, NR4—C(O), O—C(O)—NR4, NR4—C(O)—O, —CH2—, a heteroaryl, or a heteroatom group selected from O, S, S—S, S(O), S(O)2, and NR4, wherein at least two carbon atoms separate the heteroatom groups O, S, S—S, S(O), S(O)2 and NR4 from any other heteroatom group;
each T is independently absent or is alkylene, alkenylene, or alkynylene, wherein one or more —CH2— groups of the alkylene, alkenylene, or alkynylene may each independently be replaced with a heteroatom group independently selected from —O—, —S—, and —N(R4)— wherein the heteroatom groups are separated by at least 2 carbon atoms;
Y is a Cas9 ribonucleoprotein, cas9 protein, or plasmid, and
Z is absent or is —C?C—, —CH?CH—, —CH2—, —CH2—O—, —C(O)—N(R4)—, —CH2—S—, —CH2—S(O)—, —CH2—S(O)2—, —CH2—S(O)2—N(R4)—, —C(O)—O—, —CH2—N(R4)—, —CH2-N(R4)—C(O)—, —CH2—N(R4)—S(O)2—, —CH2—N(R4)—C(O)—O—, —CH2—N(R4)—C(O)—N(R4)—, —CH2—O—C(O)—, —CH2—O—C(O)—N(R4)—, —CH2—O—C(O)—O—, or aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted with R5;
each n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40, wherein if n is greater than 1, each T and each Q of each (T-Q-T-Q) is independently selected;
R2 is —OH, —N3, —N(R3)2, —N(R3)—C(O)—R3, —N(R3)—C(O)—N(R3)2, —N(R3)—C(O)—OR3, tetrazole, or triazole, wherein the tetrazole and triazole are optionally substituted with R3;
each R3 is independently —H, —(C1-C5)alkyl, halo-substituted (C1-C5)alkyl, or (C3-C6)cycloalkyl, wherein a —CH2— group of the alkyl or cycloalkyl may be replaced with a heteroatom group selected from —O—, —S—, and —N(R4)— and —CH3 of the alkyl may be replaced with a heteroatom group selected from —N(R4)2, —OR4, and —S(R4) wherein the heteroatom groups are separated by at least 2 carbon atoms; and
each R4 is independently —H, —(C1-C20)alkyl, or (C3-C6)cycloalkyl wherein one to six —CH2— groups of the alkyl or cycloalkyl separated by at least two carbon atoms may be replaced with —O—, —S—, or —N(R4)—, and —CH3 of the alkyl may be replaced with a heteroatom group selected from —N(R4)2, —OR4, and —S(R4) wherein the heteroatom groups are separated by at least 2 carbon atoms; and wherein the alkyl and cycloalkyl may be substituted with halo atoms;
each R5 is independently —H, (C3-C20)cycloalkyl or (C1-C20)alkyl wherein one to six —CH2— groups of the alkyl or cycloalkyl separated by at least two carbon atoms may be replaced with —O—, —S—, or —N(R4)—, and —CH3 of the alkyl may be replaced with a heteroatom group selected from —N(R4)2, —OR4, and —S(R4) wherein the heteroatom groups are separated by at least 2 carbon atoms; and wherein the alkyl and cycloalkyl may be substituted with one to six halo atoms;
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,969,809

THERAPEUTIC ANTIBODIES AND THEIR USES

PFIZER INC., New York, N...

1. A bispecific antibody wherein the bispecific antibody is a full-length antibody, comprising a first antibody variable domain of the bispecific antibody capable of recruiting the activity of a human immune effector cell by specifically binding to an effector antigen located on the human immune effector cell, and comprising a second antibody variable domain of the bispecific antibody capable of specifically binding to a target antigen, wherein the first antibody variable domain comprises a heavy chain variable (VH) region comprising a VH CDR1, VH CDR2, and VH CDR3 of the VH sequence shown in SEQ ID NO: 320, 322, 324, 326, 328, 330, 345, 347, 349, 351, 444, 354, 356, 378, 442, 380, 382, 384 386, 388, 390, 392, 394, 396, 398, or 400; and e a light chain variable (VL) region comprising VL CDR1, VL CDR2, and VL CDR3 of the VL sequence shown in SEQ ID NO: 319, 321, 323, 325, 327, 329, 344, 346, 348, 350, 352, 355, 377, 443, 445, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, or 399.

US Pat. No. 9,908,883

N1-PYRAZOLOSPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS

Pfizer Inc., New York, N...

1. A compound of structure
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,884,921

BISPECIFIC HETERODIMERIC DIABODIES AND USES THEREOF

Pfizer Inc., New York, N...

1. A bispecific heterodimeric diabody that specifically binds to an epitope of human P-cadherin and to an epitope of CD3 comprising
a first polypeptide chain and a second polypeptide chain, wherein:
a. the first polypeptide comprises, in the N-terminal to C-terminal direction:
i. a Domain 1, comprising a sub-Domain 1A and a sub-Domain 1B, and
ii. a first heterodimer-promoting domain; and
b. the second polypeptide chain comprises, in the N-terminal to C-terminal direction:
i. a Domain 2, comprising a sub-Domain 2B and a sub-Domain 2A and
ii. a second heterodimer-promoting domain, and
wherein sub-Domain 1A and sub-Domain 2A form a P-cadherin VL/VH binding domain comprising a variable heavy (VH) domain of
an anti-P-cadherin antibody (P-CAD VH) and a variable light (VL) domain of an anti-P-cadherin antibody (P-CAD VL), and sub-Domain
1B and sub-Domain 2B form a CD3 VL/VH binding domain comprising a VL domain of an anti-CD3 antibody (CD3 VL) and a VH binding
domain of an anti-CD3 antibody (CD3 VH); or

wherein sub-Domain 1A and sub-Domain 2A form a CD3 VL/VH binding domain comprising a CD3 VL and a CD3 VH, and sub-Domain 1B
and sub-Domain 2B form a P-cadherin VL/VH binding domain comprising a P-CAD VH and a P-CAD VL; and

wherein the first and second polypeptide chains comprise:
i. a P-CAD VL CDR1, a P-CAD VL CDR2, and a P-CAD VL CDR3 of a P-CAD VL comprising a sequence of SEQ ID NO: 1, 3, 5, 7, 9,
11, 13, 15, 17, 19, 21 or 23;

ii. a CD3 VH CDR1, a CD3 VH CDR2, and a CD3 VH CDR3 of a CD3 VH comprising a sequence of SEQ ID NO: 45 or 46;
iii. a CD3 VL CDR1, a CD3 VL CDR2, and a CD3 VL CDR3 of a CD3 VL comprising a sequence of SEQ ID NO: 47; and/or
iv. a P-CAD VH CDR1, a P-CAD VH CDR2, and a P-CAD VH CDR3 of a P-CAD VH comprising a sequence of SEQ ID NO: 2, 4, 6, 8, 10,
12, 14, 16, 18, 20, 22 or 24;

c. the sub-Domain 1A and the sub-Domain 1B are linked by a glycine-serine linker (Linker 1), and the sub-Domain 2B and the
sub-Domain 2A are linked by a glycine-serine linker (Linker 1);

d. the first heterodimer-promoting domain comprises a cysteine linker (Linker 2) on sub-Domain 1B and/or the second heterodimer-promoting
domain comprises a cysteine linker (Linker 2) on sub-Domain 2A; and

e. the first and second polypeptide chains are covalently bonded to one another by at least one disulfide bond.

US Pat. No. 9,879,022

BICYCLIC-FUSED HETEROARYL OR ARYL COMPOUNDS

Pfizer Inc., New York, N...

1. A compound of Formula IIc, IId, IIe, IIf or IIg,
wherein
R1 is C1-C6alkyl; C2-C6alkenyl; C2-C6alkynyl; —(CR3aR3b)m-(3- to 7-membered cycloalkyl); or —(CR3aR3b)m-(3- to 7-membered heterocycloalkyl) having one to three heteroatoms; wherein said alkyl, alkenyl, alkynyl, cycloalkyl or
heterocycloalkyl is optionally substituted with one to five halogen, deuterium, —OR5, —SR5, —NR11aR11b, cyano, C1-C6alkyl, C3-C6cycloalkyl or —C1-C6alkoxy;

R2 is —(CR3aR3b)m-(3- to 10-membered heterocycloalkyl) having one to three heteroatoms, wherein said heterocycloalkyl is optionally substituted
at a carbon atom with one to five R4 and wherein, if the heteroatom is N, said N is optionally substituted with R4?;

R3a and R3b are each independently hydrogen or C1-C3alkyl;

R4 for each occurrence is independently and optionally halogen, cyano, C1-C6alkyl, C2-C6alkenyl, oxo, —OR5, —SR5, —S(O)R9, —S(O)2R9, —C(O)R10, —(CR3aR3b)n-(3- to 7-membered cycloalkyl) or —(CR3aR3b)n-(4- to 7-membered heterocycloalkyl) wherein said alkyl, cycloalkyl and heterocycloalkyl are each optionally and independently
substituted with one to five deuterium, halogen, —OR5, —SR5, —NR11aR11b, cyano, C1-C6alkyl, C3-C6cycloalkyl C1-C6alkoxy or NR11aR11b; or two R4 taken together with the respective carbons to which each are bonded form a 3- to 6-membered cycloalkyl or 4- to 6-membered
heterocycloalkyl, wherein said cycloalkyl or heterocycloalkyl is optionally substituted with one to three halogen, deuterium,
—OR5, —SR5, —NR11aR11b, cyano or C1-C6alkyl or C1-C6alkoxy, wherein the alkyl or alkoxy is optionally substituted with halogen, deuterium, —OR5, —NR11aR11b, or cyano; and wherein, if a heteroatom on said heterocycloalkyl is N, said N is optionally substituted with R4?;

R4? is independently C1-C6alkyl, C2-C6alkenyl, —S(O)R9, —S(O)2R9, —C(O)R10, C(O)(CH2)tCN; wherein said alkyl is optionally substituted with NH2, cyano or halogen —(CR3aR3b)n-(3- to 7-membered cycloalkyl), —(CR3aR3b)n-(4- to 10-membered heterocycloalkyl), wherein said alkyl, alkenyl, cycloalkyl, or heterocycloalkyl is each optionally and
independently substituted with one to five deuterium, halogen, OH, cyano or C1-C6alkoxy; or R4 and R4? taken together with the respective atoms to which each are bonded form a 3- to 6-membered cycloalkyl or 4- to 6-membered heterocycloalkyl,
wherein said cycloalkyl or heterocycloalkyl is optionally substituted with one to three halogen, deuterium, —OR5, —SR5, —NR11aR11b, cyano, C1-C6alkyl or C1-C6alkoxy, wherein the alkyl or alkoxy is optionally substituted with halogen, deuterium, —OR5, —SR5, —NR11aR11b or cyano;

R5 is hydrogen or C1-C6alkyl, wherein said alkyl is optionally substituted with halogen;

R6 is —C(O)NHR7 or cyano;

R7 is hydrogen or C1-C6alkyl;

R8 is independently hydrogen, halogen, cyano, —NR11aR11b, C1-C6alkyl, 5- to 6-membered heteroaryl or 5- to 6-membered aryl, wherein said alkyl or heteroaryl or aryl is optionally substituted
with one to three halogen, —NR11aR11b, C1-C3 alkyl or oxo;

R8 is hydrogen, deuterium, halogen, cyano, —OR5, or NR11aNR11b;

R9 is —(CR3aR3b)p—(C1-C3alkyl), —(CR3aR3b)p—(4- to 6-membered cycloalkyl), —(CR3aR3b)p—(4- to 6-membered heterocycloalkyl) or —(CR3aR3b)p—(C5-C9aryl), wherein said alkyl, cycloalkyl, heterocycloalkyl or aryl is each optionally substituted with fluoro or C1-C3alkyl;

R10 is C1-C6alkyl, wherein said alkyl is optionally substituted with fluoro or cyano;

R11a and R11b are each independently hydrogen or C1-C6alkyl, wherein said alkyl is optionally substituted with OH;

m is independently 0, 1 or 2;
n is independently 0 or 1;
p is independently 0 or 1; and
t is 0, 1, 2 or 3;
or a pharmaceutically acceptable salt of said compound or a tautomer of said compound or said salt.
US Pat. No. 9,877,923

PROCESS FOR PREPARING THERAPEUTIC NANOPARTICLES

Pfizer Inc., New York, N...

1. A method of preparing a plurality of therapeutic nanoparticles, comprising:
combining a therapeutic agent, a first polymer, and an organic acid with an organic solvent to form a first organic phase
having about 1 to about 50% solids, wherein the organic acid has a pKa of less than about 3.5 at 25° C., and wherein the therapeutic agent has a solubility in a first solution consisting of the
therapeutic agent, the organic solvent, and the organic acid that is at least 5 times higher as compared to a second solution
consisting of the therapeutic agent and the organic solvent;

combining the first organic phase with a first aqueous solution to form the plurality of therapeutic nanoparticles; and
recovering the therapeutic nanoparticles by filtration,
wherein the organic solvent comprises a solvent selected from the group consisting of ethyl acetate, benzyl alcohol, methylene
chloride, chloroform, toluene, methyl ethyl ketone, dimethyl formamide, dimethyl sulfoxide, acetone, acetonitrile, acetic
acid, polysorbate 80, sorbitan monostearate 80, and combinations of two or more thereof;

wherein the organic acid comprises an acid selected from the group consisting of formic acid, oxalic acid, malonic acid, maleic
acid, malic acid, tartaric acid, citric acid, gluconic acid, aspartic acid, glutaminic acid, fumaric acid, itaconic acid,
a halogenated carboxylic acid, triflic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and combinations
thereof; and

wherein the therapeutic agent is an anticancer agent.

US Pat. No. 9,873,673

2-THIOPYRIMIDINONES

Pfizer Inc., New York, N...

1. A compound having Formula I

or a pharmaceutically acceptable salt thereof
wherein
R1 is a five to six membered aromatic ring optionally having one to three heteroatoms selected independently from nitrogen, sulfur
and oxygen or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated five to six
membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur
and oxygen; and

said R1 is optionally mono-, di-, or tri-substituted independently with cyano, halo, hydroxyl, amino, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkoxy(C1-C4)alkyl, hydroxy(C2-C4)alkoxy, carbamoyl(C1-C4)alkoxy, amino(C2-C4)alkoxy, cyano(C1-C4)alkyl, mono-N— or di-N,N—(C1-C4)alkylamino, aminocarbonyl, mono-N— or di-N,N(C1-C4)alkylaminocarbonyl, (C1-C4)alkylthio, aminosulfonyl, (C1-C4)alkylsulfinyl, (C1-C4)alkylsulfonyl, or mono-N— or di-N,N(C1-C4)alkylaminosulfonyl, wherein any of the (C1-C4)alkyl or (C1-C4)alkoxy may be optionally mono-, di- or tri-substituted with fluoro; or

wherein R1 is optionally substituted with a five to six membered aromatic ring optionally having one to three heteroatoms selected independently
from nitrogen, sulfur and oxygen;

R2 is a fully saturated, partially unsaturated or fully unsaturated one to fourteen membered straight carbon chain wherein the
carbons, other than the connecting carbon,

a. may be branched
b. may optionally be replaced with one or two heteroatoms selected independently from oxygen, sulfur and nitrogen, wherein
said sulfur is optionally mono- or di-substituted with oxo,

c. may optionally be mono-, di- or tri-substituted independently with halo,
d. may optionally be mono-substituted with hydroxy, and
e. may optionally be mono-substituted with oxo,
and wherein the carbon chain is optionally mono-substituted with Z;
wherein Z is a partially saturated, fully saturated or fully unsaturated three to seven membered ring optionally having one
to three heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially
saturated, fully saturated or fully unsaturated five to six membered rings, taken independently, optionally having one to
four heteroatoms selected independently from nitrogen, sulfur and oxygen;

wherein said Z is optionally mono-, di- or tri-substituted independently with halo, (C1-C6)alkyl, (C1-C6)alkylcarbonyl, aminothioxo, amino(C1-C6)alkylcarbonyl, hydroxyl, diaminomethylene, carbamoyl or (C1-C6)alkoxy and wherein said (C1-C6)alkyl or (C1-C6)alkoxy substituent is also optionally substituted with one to three halo, and wherein said (C1-C6)alkyl or (C2-C6)alkoxy substituent is also optionally substituted with one to three hydroxy;

with the proviso that R1 is not phenyl, and R2 is not (C1-C6)alkyl; and

with the proviso that when
R1 is phenyl and said R1 is mono-, di-, or tri-substituted independently with hydroxyethoxy, methyl, methoxy, fluoro or chloro; and

R2 is diaminomethyleneamino(C2-C4)alkyl, carbamoyl(C1-C4)alkyl, hydroxy(C2-C4)alkyl, amino(C2-C4)alkylcarbamoyl(C1-C4)alkyl, (C1-C4)alkylcarbonylamino(C2-C4)alkyl, amino(Cr C4)alkylcarbonylamino(C2-C4)alkyl, amino(C3-C4)hydroxyalkyl or amino(C2-C4)alkyl, said compounds are not included; and

with the proviso that 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide and N-(2-aminoethyl)-2-[6-(2,4-dimethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl]acetamide
or a pharmaceutically acceptable salt of said proviso's compounds are not included.

US Pat. No. 9,850,232

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

PFIZER INC., New York, N...

1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
the compound of Formula I is a compound of Formula I-c, I-d, or I-e:

Q1 is an N-containing 5- to 6-membered heteroaryl or an N-containing 5- to 6-membered heterocycloalkyl, each optionally substituted
with one R9 and further optionally substituted with 1, 2, 3, or 4 R10;

each of T1, T2, T3, T4, and T5 is independently selected from the group consisting of H, halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, C3-4 cycloalkyl, C3-4 halocycloalkyl, cyclopropylmethyl, C1-4 alkoxy, C1-4 haloalkoxy;

T6 is H, F, Cl, methyl, or C1 fluoroalkyl;

each of R1 and R2 is independently selected from the group consisting of H, halogen, —CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, —C(?O)OH, and C(?O)—O—(C1-4 alkyl), wherein each of said C1-6 alkyl and C3-6 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from halo, —OH, —CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

each of R3 and R4 is independently selected from the group consisting of H, halogen, —OH, —NO2, —CN, —SF5, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —OC(?O)R8, —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR5, wherein each of said C1-6 alkyl, C3-7 cycloalkyl, and heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the
group consisting of halogen, —CN, —OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C3-6 cycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—OR8, —C(?O)H, —C(?O)R8, —C(?O)N(R5)(R6), —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8;

or R1 and R3 together with the two carbon atoms to which they are attached form a fused N-containing 5- or 6-membered heteroaryl, a fused
N-containing 5- or 6-membered heterocycloalkyl, a fused 5- or 6-membered cycloalkyl, or a fused benzene ring, each optionally
substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, —CN, —OH, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, and C1-3 haloalkoxy;

R5 is H, C1-4 alkyl, C1-4 haloalkyl, or C3-7 cycloalkyl;

R6 is H or selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, and (C3-7 cycloalkyl)—C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, 3, or 4 substituents each independently
selected from the group consisting of —OH, —CN, C1-4 alkyl, C3-7 cycloalkyl, C1-4 hydroxylalkyl, —S—C1-4 alkyl, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

or R5 and R6 together with the N atom to which they are attached form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl,
each optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of halogen,
—OH, oxo, —C(?O)H, —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, —CN, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy;

R7 is selected from the group consisting of H, C1-4 alkyl, and C3-7 cycloalkyl;

R8 is selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, a 4- to 14-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)—C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)—C1-4 alkyl-, (C6-10 aryl)C1-4 alkyl-, and (5- to 10-membered heteroaryl)—C14 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, or 3 substituents each independently
selected from the group consisting of halogen, —CF3, —CN, —OH, oxo, —S—C1-4 alkyl, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

R9 is C1-4 alkyl, C1-4 haloalkyl, —CN, —SFS, —N(R5)(R6), C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkoxy, or C3-7 cycloalkyl, wherein each of the C1-4 alkyl and C3-7 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting
of halogen, —N(R5)(R6), C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

each R10 is independently selected from the group consisting of halogen, —OH, —CN, —SFS, —NO2, oxo, thiono, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, (C3-7 cycloalkyl)—C1-4 alkyl-, —N(R5)(R6), —N(R7)(C(?O)R8), —S(?O)2N(R5)(R6), —SR8, and —OR8, wherein each of said C1-6 alkyl, C3-7 cycloalkyl, and (C3-7 cycloalkyl)—C1-4 alkyl-, is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of
halogen, OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, [(C6-10 aryl)—C1-4 alkyloxy-optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O-C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

or R9 and an adjacent R10 together with the two ring atoms on Q1 to which they are attached form a fused benzene ring or a fused 5- or 6-membered heteroaryl, each optionally substituted with
1, 2, 3, 4, or 5 independently selectedR10a; and

each R10a is independently selected from the group consisting of halogen, —OH, —N(R5)(R6), —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—NH2, —C(?O )—N(C1-4 alkyl)2, —CN, —SF5, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy, with the proviso that

when Q1 is an optionally substituted 4H-1,2,3,4-triazol-3-yl, then Q1 is not substituted by —N(R5)(R6).

US Pat. No. 9,845,301

1,1,1-TRIFLUORO-3-HYDROXYPROPAN-2-YL CARBAMATE DERIVATIVES AND 1,1,1-TRIFLUORO-4-HYDROXYBUTAN-2-YL CARBAMATE DERIVATIVES AS MAGL INHIBITORS

PFIZER INC., New York, N...

1. A compound selected from the group consisting of:
(2R)-1,1,1-trifluoro-3-hydroxypropan-2-yl 4-[(4-fluorophenyl)sulfonyl]-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate;
(2R)-1,1,1-trifluoro-3-hydroxypropan-2-yl 4-(phenylsulfonyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate;
(2R)-1,1,1-trifluoro-3-hydroxypropan-2-yl (3R)-3-[methyl(phenylsulfonyl)amino]-1-oxa-8-azaspiro[4.5]decane-8-carboxylate;
(2R)-3,3,3-trifluoro-2-[({(3R)-3-[methyl(phenylsulfonyl)amino]-1-oxa-8-azaspiro[4.5]dec-8-yl}carbonyl)oxy]propyl dihydrogen
phosphate;

(2R)-3,3,3-trifluoro-2-[({4-[(4-fluorophenyl)sulfonyl]-1-oxa-4,9-diazaspiro[5.5]undec-9-yl}carbonyl)oxy]propyl dihydrogen
phosphate;

(2R)-1,1,1-trifluoro-3-hydroxypropan-2-yl 3-{[(4-fluorophenyl)sulfonyl](methyl)amino}-1-oxa-8-azaspiro[4.5]decane-8-carboxylate,
DIAST-1;

(2R)-1,1,1-trifluoro-3-hydroxypropan-2-yl 3-{[(4-fluorophenyl)sulfonyl](methyl)amino}-1-oxa-8-azaspiro[4.5]decane-8-carboxylate,
DIAST-2; and

(2R)-3,3,3-trifluoro-2-({[(3R)-3-{[(4-fluorophenyl)sulfonyl](methyl)amino}-1-oxa-8-azaspiro[4.5]dec-8-yl]carbonyl}oxy)propyl
dihydrogen phosphate,

or a pharmaceutically acceptable salt thereof,
or a pharmaceutically acceptable salt selected from the group consisting of:
(2R)-3,3,3-trifluoro-2-[({(3R)-3-[methyl(phenylsulfonyl)amino]-1-oxa-8-azaspiro[4.5]dec-8-yl}carbonyl)oxy]propyl phosphate,
disodium salt;

(2R)-3,3,3-trifluoro-2-[({4-[(4-fluorophenyl)sulfonyl]-1-oxa-4,9-diazaspiro[5.5]undec-9-yl}carbonyl)oxy]propyl phosphate,
disodium salt;

(2R)-3,3,3-trifluoro-2-[({4-[(4-fluorophenyl)sulfonyl]-1-oxa-4,9-diazaspiro[5.5]undec-9-yl}carbonyl)oxy]propyl phosphate,
(bis)-L-lysine salt;

(2R)-3,3,3-trifluoro-2-({[4-(phenylsulfonyl)-1-oxa-4,9-diazaspiro[5.5]undec-9-yl]carbonyl}oxy)propyl phosphate, disodium salt;
(2R)-3,3,3-trifluoro-2-[({(3R)-3-[methyl(phenylsulfonyl)amino]-1-oxa-8-azaspiro[4.5]dec-8-yl}carbonyl)oxy]propyl phosphate,
(bis)-L-lysine salt;

(2R)-3,3,3-trifluoro-2-({[4-(phenylsulfonyl)-1-oxa-4,9-diazaspiro[5.5]undec-9-yl]carbonyl}oxy)propyl phosphate, (bis)-L-lysine
salt, and

(2R)-3,3,3-trifluoro-2-({[(3R)-3-{[(4-fluorophenyl)sulfonyl](methyl)amino}-1-oxa-8-azaspiro[4.5]dec-8-yl]carbonyl}oxy)propyl
phosphate, (bis)-L-lysine salt.

US Pat. No. 9,822,097

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

PFIZER INC., New York, N...

1. A compound of Formula IA-1:
or a pharmaceutically acceptable salt thereof, wherein:
each of T1, T2, T3, and T4 is independently selected from the group consisting of H, halogen, —CN, —SF5, —OH, —N(Ra)(Rb), —C(?O)—N(Ra)(Rb), —C(?O)—Rd, C1-6alkyl, C1-6haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, —S—(C1-6 alkyl), C3-7 cycloalkyl, 4- to 7-membered heterocycloalkyl, C3-7 cycloalkoxy, 5- or 6-membered heteroaryl, cyclopropylmethyl, and cyclobutylmethyl, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —S—(C1-6 alkyl), and C1-6 alkoxy is optionally substituted with one or more substituents each independently selected from the group consisting of halogen,
—OH, —CN, —N(Ra)(Rb), C1-4alkoxy, C1-4 haloalkoxy, and —S—(C1-4 alkyl); and wherein each of the C3-7 cycloalkyl, 4- to 7-membered heterocycloalkyl, C3-7 cycloalkoxy, 5- or 6-membered heteroaryl, cyclopropylmethyl, and cyclobutylmethyl of T1, T2, and T3 is optionally substituted with one or more substituents each independently selected from the group consisting of halogen,
—OH, —CN, oxo, —N(Ra)(Rb), —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—N(Ra)(Rb), C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxylalkyl, C1-4 cyanoalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and —S—(C1-4 alkyl);

L1 is selected from the group consisting of O, S, NH, N(C1-4 alkyl), N(—C1-2 alkyl-C3-4 cycloalkyl), and N(C3-6 cycloalkyl);

each of Ra and Rb is independently selected from the group consisting of H, C1-4 alkyl, C3-7 cycloalkyl, and cyclopropylmethyl;

or Ra and Rb together with the N atom to which they are attached form 4- to 7-membered heterocycloalkyl optionally substituted with one
or more substituents each independently selected from the group consisting of halogen, —OH, —CN, oxo, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2 , —C(?O)—NH(C1-4alkyl), —C(?O)—N(C1-4 alkyl)2, C1-4 alkyl C1-4 haloalkyl, C1-4 hydroxylalkyl, C1-4 cyanoalkyl, C1-4 alkoxy, —S—(C1-4 alkyl), and C1-4 haloalkoxy;

each of Rc and Rd is independently C1-4 alkyl, C3-4 cycloalkyl-C1-2 alkyl-, or C3-4 cycloalkyl;

provided that when L1 is NH, then the ring of the formula

is substituted with at least one non-H R9 or R9A;
X1 is O or S;

each of R1, R2, R3, and R4 is independently selected from the group consisting of H, halogen, —OH, —NO2, —CN, —SF5, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, and heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the
group consisting of halogen, —CN, oxo, —OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C3-6 cycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)H, —C(?O)R8, —C(?O)N(R5)(R6), —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8;

or R2 and R4 together with the two carbon atoms to which they are attached form a fused 5- or 6-membered heteroaryl, a fused 5- or 6-membered
heterocycloalkyl ring, a fused 5- or 6-membered cycloalkyl ring, or a fused benzene ring, wherein each of the fused rings
is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, —CN,
—OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, and C1-4 haloalkoxy, and wherein the fused heterocycloalkyl ring or fused cycloalkyl ring is further optionally substituted with 1,
2, or 3 oxo;

R5 is H, C1-4 alkyl, C1-4 haloalkyl, or C3-7 cycloalkyl;

R6 is H or selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, 3, or 4 substituents each independently
selected from the group consisting of —OH, —CN, C1-4 alkyl, C3-7 cycloalkyl, C1-4 hydroxylalkyl, —S—C1-4 alkyl, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

or R5 and R6 together with the N atom to which they are attached form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl,
each optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of halogen,
—OH, oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)OH, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, —CN, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy;

R7 is selected from the group consisting of H, C1-4 alkyl, and C3-7 cycloalkyl;

R8 is selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, or 3 substituents each independently
selected from the group consisting of halogen, —CF3, —CN, —OH, oxo, —S—C1-4 alkyl, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

each R9 is independently selected from the group consisting of halogen, —CN, —SF5, —NO2, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, —N(R5)(R6), —N(R7)(C(?O)R8), —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O) —OR8, —SR8, and —OR8, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl- is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of
halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

each of R9A is independently selected from the group consisting of H, C1-6 alkyl, C1-6 hydroxylalkyl, C2-6 alkenyl, —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR15, —C(R14)2—OH, —C(R14)2—OS(?O)2H, —C(R14)2—OP(?O)(OH)2, —C(R14)2—OR15, —C(R14)2—OC(?O)—R15, —C(R14)2—N(R5)(R6),

each R14 is independently H or selected from the group consisting of C1-10 alkyl, C3-14 cycloalkyl, C2-10 alkenyl, C2-10 alkynyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-14 cycloalkyl)-C1-10 alkyl-, (4- to 14-membered heterocycloalkyl)-C1-10 alkyl-, (C6-10 alkyl)-C1-10 alkyl-, (5- to 10-membered heteroaryl)-C1-10 alkyl-, wherein each of the selections of the group is optionally substituted with 1, 2, 3, or 4 substituents each independently
selected from the group consisting of halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —N(R7)C(?O)R8, —N(R7)C(?O)OR8, —N(R7)S(?O)2R8, —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR8, —OR8, —S(?O)2—R8, C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —NHC(?O)H, C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

R15 is selected from the group consisting of C1-20 alkyl, C3-14 cycloalkyl, C2-20 alkenyl, C2-20 alkynyl, C6-10 aryl, 4- to 14-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-14 cycloalkyl)-C1-20 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-20 alkyl-, (C6-10 aryl)-C1-20 alkyl-, (5- to 10-membered heteroaryl)-C1-20 alkyl-, wherein each of the selections of the group is optionally substituted with 1, 2, 3, or 4 substituents each independently
selected from the group consisting of halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —N(R7)C(?O)R8, —N(R7)C(?O)OR8, —N(R7)S(?O)2R8, —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR8, —OR8, —S(?O)2-R8, C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —NHC(?O)H, C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy; and

t1 is 0, 1, or 2.

US Pat. No. 9,771,379

N-(2-(2-AMINO-6-SUBSTITUTED-4,4A,5,6-TETRAHYDROPYRANO[3,4-D][1,3]OXAZIN-8A(8H)-YL)-THIAZOL-4-YL) AMIDES

PFIZER INC., New York, N...

1. A compound of Formula I

wherein
R1 is a 5- to 6-membered heteroaryl, having one to four heteroatoms independently selected from N, O or S, wherein at least one
of the heteroatoms is N and wherein said N is optionally substituted with R6; and wherein said 5- to 6-membered heteroaryl is optionally substituted on carbon with one to three R5;

R2 and R3 are each independently selected from the group consisting of hydrogen, C1-3alkyl, C3-6cycloalkyl and 3- to 7-membered heterocycloalkyl; wherein the C1-3alkyl is optionally and independently with one to three fluoro or C1-3alkoxy, and the C3-6cycloalkyl and 3- to 7-membered heterocycloalkyl are each optionally and independently substituted with one to three fluoro,
C1-3alkyl or C1-3alkoxy;

or R2 and R3 taken together with the carbon to which they are attached form a C3-6 cycloalkyl ring or a 3- to 7-membered heterocycloalkyl, each of which is optionally and independently substituted with one
to three fluoro, C1-3alkyl or C1-3alkoxy;

R4 is hydrogen or C1-3alkyl optionally substituted with one to three fluoro;

X is CH2 or a bond;

R5 at each occurrence is independently selected from the group consisting of halo, hydroxy, cyano, C1-6alkyl, C1-6alkoxy, C3-6alkenyl, C3-6alkenyloxy, C3-6alkynyl, C3-6alkynyloxy, C1-6alkoxy-C1-6alkyl, C3-6cycloalkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C3-6cycloalkyl-C1-6alkoxy, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl; wherein said C1-6alkyl, C1-6alkoxy, C3-6alkenyl, C3-6alkenyloxy, C3-6alkynyl, C3-6alkynyloxy, C1-6alkoxy-C1-6alkyl, C3-6cycloalkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C3-6cycloalkyl-C1-6alkoxy, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl are each optionally substituted
with one to three substituents independently selected from fluoro, chloro, hydroxy, cyano, methyl, fluoromethyl, difluoromethyl,
trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy and trifluoromethoxy; and

R6 is hydrogen or C1-6alkyl;

or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer.
US Pat. No. 9,724,402

NEISSERIA MENINGITIDIS COMPOSITION AND METHODS THEREOF

Pfizer Inc., New York, N...

1. An isolated non-lipidated and non-pyruvylated polypeptide comprising an amino acid sequence set forth as SEQ ID NO: 68,
wherein an N-terminal cysteine at position 1 is deleted, as compared to SEQ ID NO: 15.
US Pat. No. 9,695,171

3,4-DISUBSTITUTED-1 H-PYRROLO[2,3-B]PYRIDINES AND 4,5-DISUBSTITUTED-7H-PYRROLO[2,3-C]PYRIDAZINES AS LRRK2 INHIBITORS

Pfizer Inc., New York, N...

1. A compound selected from the group consisting of:
3-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
2-fluoro-3-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]imidazo[1,2-b]pyridazine;
1-methyl-4-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-pyrrole-2-carbonitrile;
1-methyl-4-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-imidazole-2-carbonitrile;
1-methyl-4-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-c]pyridazin-5-yl]-1H-pyrrole-2-carbonitrile;
4-[2-chloro-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1-methyl-1H-pyrrole-2-carbonitrile;
3-[2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[6-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[5-(hydroxymethyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(3-cyanophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;
4-(3,6-dihydro-2H-pyran-4-yl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(1-methyl-1H-pyrazol-4-yl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-cyano-2-fluorophenyl)-4-(dimethylamino)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;
3-(5-fluoro-2-methoxyphenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-fluoro-5-methoxyphenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
2-methyl-3-(1-methyl-1H-pyrazol-4-yl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
2-fluoro-3-[6-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
6-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridine-2-carbonitrile;
3-(3-chlorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-chloro-5-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(2,5-difluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(2-chlorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(2,3-difluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(2-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(5-chloro-2-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
{3-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl}methanol;
{4-fluoro-3-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl}methanol;
3-[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-methoxyphenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-chloro-2-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(morpholin-4-yl)-3-(2,3,5-trifluorophenyl)-1H-pyrrolo[2,3-b]pyridine;
3-(3,5-difluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(2-chloropyridin-3-yl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(morpholin-4-yl)-3-phenyl-1H-pyrrolo[2,3-b]pyridine;
3-(2,4-difluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-fluoro-5-methylphenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-fluoro-5-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(2,3-difluoro-6-methoxyphenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
2-fluoro-5-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(5-methoxypyridin-3-yl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
6-[2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridine-2-carbonitrile;
3-(1-methyl-1H-pyrazol-4-yl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;
3-(3-cyano-2-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;
3-(3-fluoro-5-methylphenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;
4-fluoro-3-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-fluoro-4-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(hydroxymethyl)-5-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(4-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
2-methyl-3-(5-methylpyridin-3-yl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-chlorophenyl)-2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
2-methyl-4-(morpholin-4-yl)-3-phenyl-1H-pyrrolo[2,3-b]pyridine;
3-(2-fluorophenyl)-2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-fluorophenyl)-2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-fluoro-5-[2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
1-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-ol;
4-[(2S)-2-methylmorpholin-4-yl]-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(3,3-difluoropiperidin-1-yl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
{1-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl}methanol;
3-(1-methyl-1H-pyrazol-4-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrrolo[2,3-b]pyridine;
N,N-dimethyl-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-amine;
3-(1-methyl-1H-pyrazol-4-yl)-4-(thiomorpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(3,3-difluoropyrrolidin-1-yl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-[4-(3,6-dihydro-2H-pyran-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[4-(3-hydroxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-{4-[2-(methoxymethyl)morpholin-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
4-(morpholin-4-yl)-3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-[4-(1,4-oxazepan-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[4-(4-hydroxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[4-(3-methoxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[4-(6-oxa-3-azabicyclo[3.1.1]hept-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-{4-[(3R,4R)-3,4-difluoropyrrolidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
3-[4-(4-fluoropiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-{4-[(3R)-3-fluoropyrrolidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
3-{4-[(2R)-2-methylmorpholin-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
3-[4-(pyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-{4-[(3S)-3-fluoropyrrolidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
3-[4-(3,3-difluoropiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-{4-[(2S)-2-methylmorpholin-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
4-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-2(1H)-one;
methyl 3-(3-cyanophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate;
3-[5-(cyanomethyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[5-(methoxymethyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
1-methyl-4-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-pyrrole-2-carboxamide;
4-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-pyrrole-2-carbonitrile;
1-methyl-4-[2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-pyrrole-2-carbonitrile;
3-[4-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(1-methyl-1H-pyrazol-4-yl)-4-phenyl-1H-pyrrolo[2,3-b]pyridine;
3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-c]pyridazin-5-yl]benzonitrile;
3-[3-(3-cyanophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-N-cyclopropylbenzamide;
2-fluoro-3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-c]pyridazin-5-yl]benzonitrile;
3-[4-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
4-(3,4-difluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(2,5-difluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(2,3-difluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(3-chlorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(2-fluoro-3-methoxyphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-[3-(3-cyanophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-N-methylbenzenesulfonamide;
4-cyclopropyl-3-(2,3-difluoro-6-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;
3-[4-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(1-methyl-1H-pyrazol-4-yl)-4-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(3,5-difluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(3-fluoro-4-methoxyphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(2-fluoro-4-methoxyphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(furan-3-yl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
5-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,3-benzothiazole;
{3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]phenyl}acetonitrile;
3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]benzonitrile;
5-(1-methyl-1H-pyrazol-4-yl)-4-(morpholin-4-yl)-7H-pyrrolo[2,3-c]pyridazine;
4-[3-(m ethoxymethyl)phenyl]-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine; and
3-{4-[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,688,698

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

PFIZER INC., New York, N...

1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
L1 is O;


Q1 is a moiety of


R9 is halogen, C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, —CN, —N(R5)(R6), C1-6 alkoxy, C1-6 haloalkoxy, or C3-7 cycloalkoxy, wherein each of the C1-4 alkyl and C3-7 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting
of halogen, —N(R5)(R6), C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

each R10 is independently selected from the group consisting of halogen, —OH, —CN, —NO2, oxo, thiono, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C2-4 alkenyl-, —N(R5)(R6), —N(R7)(C(?O)R8), —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, and —OW, wherein each of said C1-6 alkyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C2-4 alkenyl- is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of
halogen, OH, —CN, —NC2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, (C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl, oxo, —C(?O)H, —O(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

R11 is H, C1-4 alkyl, C1-4 haloalkyl, (C1-2 alkoxy)-C1-4 alkyl-, or C3-7 cycloalkyl;

m is 0, 1, 2, 3, or 4;
X1 is O, S, NH, N(C1-4 alkyl), N(cyclopropyl), or N(—CH2-cyclopropyl);

X2 is N or C-T2;

X3 is N or C-T3;

provided that when X1 is O or S, then at least one of X2 and X3 is not N;

X4 is N or C-T4;

T1 is H, F, Cl, methyl, or C1 fluoroalkyl;

each of T2, T3, and T4 is independently selected from the group consisting of H, halogen, —CN, methoxy, C1 fluoroalkoxy, methyl, and C1 fluoroalkyl;

each of R1 and R2 is independently selected from the group consisting of H, halogen, —CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy, and C3-6, cycloalkyl;

each of R3 and R4 is independently selected from the group consisting of H, halogen, —CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, G cycloalkyl, and C1-6 alkoxy;

R5 is H, C1-4 alkyl, C1-4 haloalkyl, or C3-7 cycloalkyl;

R6 is H or selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, 3, or 4 substituents each independently
selected from the group consisting of —OH, —CN, C1-4 alkyl, C3-7 cycloalkyl, C1-4 hydroxylalkyl, —S—C1-4 alkyl, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

or R5 and R6 together with the N atom to which they are attached form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl,
each optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of halogen,
—OH, oxo, —C(?O)H, —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, —CN, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy;

R7 is selected from the group consisting of H, C1-4 alkyl, and C3-7 cycloalkyl; and

R8 is selected from the group consisting of C1-6 alkyl and C3-7 cycloalkyl, wherein each of the selections from the group is optionally substituted with 1, 2, or 3 substituents each independently
selected from the group consisting of halogen, —CF3, —CN, —OH, oxo, —S—C1-4 alkyl, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
with the proviso that when X1 is NH, N(C1-4 alkyl), N(cyclopropyl), or N(—CH2-cyclopropyl), then X4 is C-T4.

US Pat. No. 9,663,526

AMINOPYRIMIDINYL COMPOUNDS

Pfizer Inc., New York, N...

1. A compound having the structure:

or a pharmaceutically acceptable salt thereof, wherein X is N or CR, where R is hydrogen, deuterium, C1-C4 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, aryl, heteroaryl, aryl(C1-C6 alkyl), CN, amino, alkylamino, dialkylamino, CF3, or hydroxyl;

A is selected from the group consisting of a bond, C?O, —SO2—, —(C?O)NR0—, and —(CRaRb)q—, where R0 is H or C1-C4 alkyl, and Ra and Rb are independently hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, aryl, aryl(C1-C6 alkyl), heteroaryl, (C1-C6 alkyl)heteroaryl, heteroaryl(C1-C6 alkyl), and heterocyclic(C1-C6 alkyl);

A? is selected from the group consisting of a bond, C?O, —SO2—, —(C?O)NR0?, —NR0?(C?O)—, and —(CRa?Rb?)q—, where R0? is H or C1-C4 alkyl, and Ra? and Rb? are independently hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, aryl, aryl(C1-C6 alkyl), heteroaryl, (C1-C6 alkyl)heteroaryl, heteroaryl(C1-C6 alkyl), and heterocyclic(C1-C6 alkyl);

Z is —(CH2)h— or a bond, where one or more methylene units are optionally substituted by one or more C1-C3 alkyl, CN, OH, methoxy, or halo, and where said alkyl may be substituted by one or more fluorine atoms;

R1 and R1? are independently selected from the group consisting of hydrogen, deuterium, C1-C4 alkyl, C3-C6 cycloalkyl, aryl, heteroaryl, aryl(C1-C6 alkyl), CN, amino, alkylamino, dialkylamino, alkoxy, heteroaryl(C1-C6 alkyl), and heterocyclic(C1-C6 alkyl), wherein said alkyl, aryl, cycloalkyl, heterocyclic, or heteroaryl is further optionally substituted with one or more
substituents selected from the group consisting of C1-C6 alkyl, halo, CN, hydroxy, methoxy, amino, C1-C4 alkyl amino, di(C1-C4 alkyl)amino, CF3, —SO2—(C1-C6 alkyl), and C3-C6 cycloalkyl;

R2 is selected from the group consisting of hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, halo, and cyano, where said alkyl may be substituted by one or more fluorine atoms;

R3 is selected from the group consisting of hydrogen, deuterium, and amino;

R4 is monocyclic or bicyclic aryl or monocyclic or bicyclic heteroaryl wherein said aryl or heteroaryl is optionally substituted
with one or more substituents selected from the group consisting of C1-C6 alkyl, heterocycloalkyl, halo, CN, hydroxy, —CO2H, C1-C6 alkoxy, amino, —N(C1-C6 alkyl)(CO)(C1-C6 alkyl), —NH(CO)(C1-C6 alkyl), —(CO)NH2, —(CO)NH(C1-C6 alkyl), —(CO)N(C1-C6 alkyl)2, —(C1-C6 alkyl)amino, —N(C1-C6 alkyl)2, —SO2—(C1-C6 alkyl), —(SO)NH2, and C3-C6 cycloalkyl, where said alkyl, cycloalkyl, alkoxy, or heterocycloalkyl may be substituted by one or more C1-C6 alkyl, halo, CN, OH, alkoxy, amino, —CO2H, —(CO)NH2, —(CO)NH(C1-C6 alkyl), or —(CO)N(C1-C6 alkyl)2, and where said alkyl may be further substituted by one or more fluorine atoms;

R5 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 alkoxy, and hydroxyl;

h is 1, 2 or 3; j and k are independently 0, 1, 2, or 3; m and n are independently 0, 1 or 2; and, q is 0, 1 or 2.

US Pat. No. 9,527,831

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

PFIZER INC., New York, N...

1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
each of T1, T2, T3, and T4 is independently selected from the group consisting of H, halogen, —CN, —SF5, —OH, —N(Ra)(Rb), —C(?O)—N(Ra)(Rb), —C(?O)—ORc, —C(?O)—Rd, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, —S—(C1-6 alkyl), C3-7 cycloalkyl, 4- to 7-membered heterocycloalkyl, C3-7 cycloalkoxy, 5- or 6-membered heteroaryl, cyclopropylmethyl, and cyclobutylmethyl, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —S—(C1-6 alkyl), and C1-6 alkoxy is optionally substituted with one or more substituents each independently selected from the group consisting of halogen,
—OH, —CN, —N(Ra)(Rb), C1-4 alkoxy, C1-4 haloalkoxy, and —S—(C1-4 alkyl); and wherein each of the C3-7 cycloalkyl, 4- to 7-membered heterocycloalkyl, C3-7 cycloalkoxy, 5- or 6-membered heteroaryl, cyclopropylmethyl, and cyclobutylmethyl of T1, T2, and T3 is optionally substituted with one or more substituents each independently selected from the group consisting of halogen,
—OH, —CN, oxo, —N(Ra)(Rb), —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—N(Ra)(Rb), C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxylalkyl, C1-4 cyanoalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and —S—(C1-4 alkyl);

L1 is selected from the group consisting of O, S, NH, N(C1-4 alkyl), N(—C1-2 alkyl-C3-4 cycloalkyl), and N(C3-6 cycloalkyl);

each of Ra and Rb is independently selected from the group consisting of H, C1-4 alkyl, C3-7 cycloalkyl, and cyclopropylmethyl;

or Ra and Rb together with the N atom to which they are attached form 4- to 7-membered heterocycloalkyl optionally substituted with one
or more substituents each independently selected from the group consisting of halogen, —OH, —CN, oxo, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —C(?O)OH, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—NH(C1-4 alkyl), —C(?O)—N(C1-4 alkyl)2, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxylalkyl, C1-4 cyanoalkyl, C1-4 alkoxy, —S—(C1-4 alkyl), and C1-4 haloalkoxy;

each of Rc and Rd is independently C1-4 alkyl, C3-4 cycloalkyl-C1-2 alkyl-, or C3-4 cycloalkyl;

Q1 is selected from the group consisting of Q1b, Q1c Q1d, and Q1e:


provided (a) that a ring carbon atom of the Q1 ring is attached to the benzene ring of Formula I and (b) that when L1 is NH, then the Q1 ring is substituted with at least one non-H R9, R10, R11, R12, R13, R9A, R10A, R10B, R11A, R12A, or R13A;

each of X1 and X2 is independently O or S;

each of R1, R2, R3, and R4 is independently selected from the group consisting of H, halogen, —OH, —NO2, —CN, —SF5, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, and heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the
group consisting of halogen, —CN, oxo, —OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C3-6 cycloalkyl, —N(R5)(R6), —N(R7)(C(?O)R8), —C(?O)—OR8, —C(?O)H, —C(?O)R8, —C(?O)N(R5)(R6), —N(R7)(S(?O)2R8), —S(?O)2—N(R5)(R6), —SR8, and —OR8;

or R2 and R4 together with the two carbon atoms to which they are attached form a fused 5- or 6-membered heteroaryl, a fused 5- or 6-membered
heterocycloalkyl ring, a fused 5- or 6-membered cycloalkyl ring, or a fused benzene ring, wherein each of the fused rings
is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, —CN,
—OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, and C1-4 haloalkoxy, and wherein the fused heterocycloalkyl ring or fused cycloalkyl ring is further optionally substituted with 1,
2, or 3 oxo;

R5 is H, C1-4 alkyl, C1-4 haloalkyl, or C3-7 cycloalkyl;

R6 is H or selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, 3, or 4 substituents each independently
selected from the group consisting of —OH, —CN, C1-4 alkyl, C3-7 cycloalkyl, C1-4 hydroxylalkyl, —S—C1-4 alkyl, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

or R5 and R6 together with the N atom to which they are attached form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl,
each optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of halogen,
—OH, oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)OH, —C(?O)—O—C1-4 alkyl, —C(?O)—NH2, —C(?O)—N(C1-4 alkyl)2, —CN, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy;

R7 is selected from the group consisting of H, C1-4 alkyl, and C3-7 cycloalkyl;

R8 is selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with 1, 2, or 3 substituents each independently
selected from the group consisting of halogen, —CF3, —CN, —OH, oxo, —S—C1-4 alkyl, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

each R9 and R12 is independently selected from the group consisting of halogen, —OH, —CN, —SF5, —NO2, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, —N(R5)(R6), —N(R7)(C(?O)R8), —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR8, and —OR8, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl- is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of
halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

each of R10, R11 and R13 is independently selected from the group consisting of halogen, —OH, —CN, —SF5, —NO2, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, —N(R5)(R6), —N(R7)(C(?O)R8), —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR8, and —OR8, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl- is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of
halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

each of R9A and R10A is independently selected from the group consisting of H, C1-6 alkyl, C1-6 hydroxylalkyl, C2-6 alkenyl, —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR15, —C(R14)2—OH, —C(R14)2—OS(?O)2H, —C(R14)2—OP(?O)(OH)2, —C(R14)2—OR15, —C(R14)2—OC(?O)—R15, —C(R14)2—N(R5)(R6),

each of R10B, R11A, R12A, and R13A is independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxylalkyl, C3-7 cycloalkyl, C3-6 alkenyl, C3-6 alkynyl, C6-10 aryl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, (5- to 10-membered heteroaryl)-C1-4 alkyl-, —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, and —C(?O)—OR8, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of
halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —S—(C1-4 alkyl), —S(?O)2—(C1-4 alkyl), C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —C(?O)—C1-4 alkyl, —C(?O)O—C1-4 alkyl, —C(?O)NH2, —NHC(?O)H, —NHC(?O)—(C1-4 alkyl), —OC(?O)—C1-4 alkyl, C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

each R14 is independently H or selected from the group consisting of C1-10 alkyl, C3-14 cycloalkyl, C2-10 alkenyl, C2-10 alkynyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-14 cycloalkyl)-C1-10 alkyl-, (4- to 14-membered heterocycloalkyl)-C1-10 alkyl-, (C6-10 aryl)-C1-10 alkyl-, (5- to 10-membered heteroaryl)-C1-10 alkyl-, wherein each of the selections of the group is optionally substituted with 1, 2, 3, or 4 substituents each independently
selected from the group consisting of halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —N(R7)C(?O)R8, —N(R7)C(?O)OR8, —N(R7)S(?O)2R8, —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR8, —S(?O)2—R8, C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —NHC(?O)H, C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

R15 is selected from the group consisting of C1-20 alkyl, C3-14 cycloalkyl, C2-20 alkenyl, C2-20 alkynyl, C6-10 aryl, 4- to 14-membered heterocycloalkyl, 5- to 10-membered heteroaryl, (C3-14 cycloalkyl)-C1-20 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-20 alkyl-, (C6-10 aryl)-C1-20 alkyl-, (5- to 10-membered heteroaryl)-C1-20 alkyl-, wherein each of the selections of the group is optionally substituted with 1, 2, 3, or 4 substituents each independently
selected from the group consisting of halogen, —OH, —CN, —NO2, C1-4 alkyl, C1-4 hydroxylalkyl, C1-4 alkoxy, —N(R5)(R6), —N(R7)C(?O)R8, —N(R7)C(?O)OR8, —N(R7)S(?O)2R8, —S(?O)2N(R5)(R6), —C(?O)—N(R5)(R6), —C(?O)—R8, —C(?O)—OR8, —SR8, —S(?O)2—R8, C6-10 aryloxy, [(C6-10 aryl)-C1-4 alkyloxy- optionally substituted with 1 or 2 C1-4 alkyl], oxo, —C(?O)H, —NHC(?O)H, C3-7 cycloalkyl, a 5- or 6-membered heteroaryl, C1-4 haloalkyl, and C1-4 haloalkoxy;

t1 is 0, 1, or 2;
t2 is 0 or 1; and
t3 is 0, 1, or 2.
US Pat. No. 10,131,669

PYRAZOLOPYRIMIDINE COMPOUNDS

Pfizer Inc., New York, N...

1. A compound selected from the group consisting of:Azetidin-1-yl[3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]methanone;
3-(4-Chlorophenyl)-N-propylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-3-fluorophenyl)pyrazolo[1,5-a]pyrimidin-2-amine;
N-[3-(4-Chloro-3-fluorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]butanamide;
3-(4-Chloro-3-fluorophenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-Chloro-2-methylphenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-Chlorophenyl)-N-cyclopropyl-6-fluoropyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-Chlorophenyl)-N-(pyrimidin-2-yl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
Azetidin-1-yl[3-(4-chlorophenyl)-6-fluoropyrazolo[1,5-a]pyrimidin-2-yl]methanone;
3-(4-chlorophenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chlorophenyl)-N-(1-methylcyclopropyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
azetidin-1-yl[3-(4-chloro-3-fluorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]methanone;
3-(5-chloro-2-fluorophenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-2-fluorophenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
4-[2-(azetidin-1-ylcarbonyl)pyrazolo[1,5-a]pyrimidin-3-yl]-2-fluorobenzonitrile;
3-(4-cyano-5-fluoro-2-methylphenyl)-N-ethylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-5-fluoro-2-methylphenyl)-N-ethylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-2-methylphenyl)-N-ethylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-2,5-difluorophenyl)-N-ethylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
azetidin-1-yl[3-(4-chloro-2-fluorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]methanone;
azetidin-1-yl[3-(4-chloro-2-methylphenyl)pyrazolo[1,5-a]pyrimidin-2-yl]methanone;
3-(4-cyano-5-fluoro-2-methylphenyl)-N-cyclobutylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-cyano-5-fluoro-2-methylphenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-5-fluoro-2-methylphenyl)-N-cyclobutylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-5-fluoro-2-methylphenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chlorophenyl)-N-(propan-2-yl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
N-(bicyclo[1.1.1]pent-1-yl)-3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-3-fluorophenyl)-N-[(1R,2S)-2-fluorocyclopropyl]pyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(5-chloropyridin-3-yl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
N-[3-(4-chloro-3-fluorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzamide;
3-(3-chlorophenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
N-cyclopropyl-3-(3,4-dichlorophenyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-3,5-difluorophenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chlorophenyl)-N-(2-methylcyclopropyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chlorophenyl)-N-cyclopropyl-N-methylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chlorophenyl)-N-[1-(trifluoromethyl)cyclopropyl]pyrazolo[1,5-a]pyrimidine-2-carboxamide;
azetidin-1-yl{3-[2-(difluoromethoxy)pyridin-4-yl]pyrazolo[1,5-a]pyrimidin-2-yl}methanone;
N-cyclopropyl-3-[2-(difluoromethoxy)pyridin-4-yl]pyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-3-fluorophenyl)-N-(2,2-difluorocyclopropyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chlorophenyl)-N-(2,2-difluorocyclopropyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
azetidin-1-yl[3-(4-chloro-3,5-difluorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]methanone;
N-cyclopropyl-3-(2-methoxypyridin-4-yl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(1,3-benzoxazol-6-yl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(6-cyanopyridin-3-yl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-cyano-2,5-difluorophenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
4-[2-(azetidin-1-ylcarbonyl)pyrazolo[1,5-a]pyrimidin-3-yl]-2,5-difluorobenzonitrile;
3-(4-chloro-2,5-difluorophenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
azetidin-1-yl[3-(3-chlorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]methanone;
azetidin-1-yl[3-(4-chloro-2,5-difluorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]methanone;
3-[2-(difluoromethoxy)pyridin-4-yl]-N-ethylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-2-methylphenyl)-N-(propan-2-yl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chlorophenyl)-N-ethylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-3-fluorophenyl)-N-ethylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-5-fluoro-2-methylphenyl)-N-(propan-2-yl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-2-methylphenyl)-N-cyclopropyl-6-fluoropyrazolo[1,5-a]pyrimidine-2-carboxamide;
N-cyclopropyl-3-[2-(difluoromethoxy)pyridin-4-yl]-6-fluoropyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-3,5-difluorophenyl)-N-cyclopropyl-6-fluoropyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-2,3-difluorophenyl)-N-cyclopropyl-6-fluoropyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-3-fluorophenyl)-N-cyclopropyl-6-fluoropyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(1,3-benzoxazol-5-yl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
azetidin-1-yl[3-(4-chloro-5-fluoro-2-methylphenyl)pyrazolo[1,5-a]pyrimidin-2-yl]methanone;
4-[2-(azetidin-1-ylcarbonyl)pyrazolo[1,5-a]pyrimidin-3-yl]-2,6-difluorobenzonitrile;
N-cyclopropyl-6-fluoro-3-(3-fluoro-4-methylphenyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-5-fluoro-2-methylphenyl)-N-cyclopropyl-6-fluoropyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(1,3-benzoxazol-5-yl)-N-cyclopropyl-6-fluoropyrazolo[1,5-a]pyrimidine-2-carboxamide;
azetidin-1-yl[3-(4-chloro-3-fluorophenyl)-6-fluoropyrazolo[1,5-a]pyrimidin-2-yl]methanone;
3-(4-cyano-5-fluoro-2-methylphenyl)-N-cyclopropyl-6-fluoropyrazolo[1,5-a]pyrimidine-2-carboxamide;
4-[2-(azetidin-1-ylcarbonyl)-6-fluoropyrazolo[1,5-a]pyrimidin-3-yl]-2-fluorobenzonitrile;
4-[2-(azetidin-1-ylcarbonyl)pyrazolo[1,5-a]pyrimidin-3-yl]-2-fluoro-5-methylbenzonitrile;
N-cyclopropyl-3-(3-fluoro-4-methylphenyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-2,3-difluorophenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chloro-2,5-difluorophenyl)-N-cyclopropyl-6-fluoropyrazolo[1,5-a]pyrimidine-2-carboxamide;
3-(4-chlorophenyl)-N-methylpyrazolo[1,5-a]pyrimidine-2-carboxamide;
azetidin-1-yl[3-(5-chloro-2-fluorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]methanone;
4-[2-(azetidin-1-ylcarbonyl)pyrazolo[1,5-a]pyrimidin-3-yl]-3-fluorobenzonitrile;
3-(4-cyano-2-fluorophenyl)-N-cyclopropylpyrazolo[1,5-a]pyrimidine-2-carboxamide; or
a pharmaceutically acceptable salt thereof.

US Pat. No. 9,920,043

CRYSTALLINE FORM OF 6-[(4R)-4-METHYL-1,2-DIOXIDO-1,2,6-THIADIAZINAN-2-YL]IOSOQUINOLINE-1-CARBONITRILE

Pfizer Inc., New York, N...

1. A crystalline form of 6-[(4R)-4-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl]isoquinoline-1-carbonitrile having an X-ray
powder diffraction pattern with characteristic peaks expressed in degrees 2-theta (±0.2° 2-theta) at 7.8, 10.9 and 15.2.

US Pat. No. 9,902,691

INTERMEDIATES AND METHODS FOR SYNTHESIZING CALICHEAMICIN DERIVATIVES

Pfizer Inc., New York, N...

1. A compound of Formula I

wherein R12 is selected from straight and branched-chain C1-C8 alkyl;

each R10 is independently selected from hydrogen, R12 and —OR12;

R8 and R9 are each independently selected from hydrogen and straight and branched-chain C1-C8 alkyl, wherein each said alkyl for R8 and R9 is independently optionally substituted by —NH2, —NHR11, —NR11R13, —OR11, —OH, or —SR11, wherein each R11 and each R13 are independently selected from straight and branched-chain C1-C5 alkyl;

r is an integer 0 or 1;
G is oxygen or sulfur;
Z1 is H or straight or branched-chain C1-C5 alkyl;

Ar is 1,2-, 1,3-, or 1,4-phenylene optionally substituted with one, two or three groups independently selected from straight
or branched-chain C1-C6 alkyl, —OR14, —SR14, halogen, nitro, —COOR14, —C(?O)NHR14, —O(CH2)nCOOR14, —S(CH2)nCOOR14, —O(CH2)nC(?O)NHR14, and —S(CH2)nC(?O)NHR14, or Ar is a 1,2-, 1,3-, 1,4-, 1,5-, 1,6-, 1,7-, 1,8-, 2,3-, 2,6-, or 2,7-naphthylidene optionally substituted with one, two,
three, or four groups independently selected from straight or branched-chain C1-C6 alkyl, —OR14, —SR14, halogen, nitro, —COOR14, —C(?O)NHR14, —O(CH2)nCOOR14, —S(CH2)nCOOR14, —O(CH2)nC(?O)NHR14, and —S(CH2)nC(?O)NHR14;

wherein each R14 is independently selected from (C1-C5)alkyl and each R14 is independently optionally substituted with one or two groups selected from —OH, —(C1-C4)alkyl, and —S(C1-C4)alkyl;

each n is an integer independently selected from 0, 1, 2, 3, 4, and 5;
W is selected from —O—, —S—, —C(?O)NH—, —NHC(?O)—, and —NR15—, wherein R15 is a (C1-C5)alkyl and R15 is optionally substituted with one or two groups selected from —OH, —(C1-C4)alkyl, and —S(C1-C4)alkyl; and

Y is a straight or branched-chain (C1-C6)alkylene group or a straight or branched-chain (C2-C6)alkenylene group.

US Pat. No. 9,828,428

ANTI-IL-13 RECEPTOR ALPHA 2 ANTIBODIES AND ANTIBODY-DRUG CONJUGATES

Pfizer Inc., New York, N...

1. An isolated antibody or antigen-binding fragment thereof that specifically binds to human IL-13 receptor alpha 2 (IL-13-R?2)
wherein the antibody comprises a heavy chain variable region and a light chain variable region comprising
a heavy chain variable region comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 1 and a light chain variable region comprising
a CDR1, CDR2, and CDR3 of SEQ ID NO: 5.

US Pat. No. 9,777,076

SACCHARIDES AND USES THEREOF

Pfizer Inc., New York, N...

1. A non-naturally occurring polysaccharide comprising a legionaminic acid moiety, a N-acetylgalactosamine moiety, a galactose
moiety, and a glucose moiety, wherein the polysaccaride comprises a repeating unit of a structure represented by:
wherein Leg is a legionaminic acid moiety, Gal is a galactose moiety, Glc is a glucose moiety, and GalNAc is a N-acetylgalactosamine
moiety, and wherein n is an integer from 40 to 60, and wherein the polysaccaride is conjugated to a carrier protein.
US Pat. No. 9,770,441

CRYSTALLINE SOLID FORMS OF 6-CARBOXY-2-(3,5-DICHLOROPHENYL)-BENZOXAZOLE

Pfizer Inc., New York, N...

1. A crystalline form of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole, wherein said crystalline form has an analytical parameter
selected from the group consisting of
a solid state NMR spectrum comprising 13C chemical shifts (ppm) at 120.8±0.2 and 127.7±0.2,
a powder X-ray diffraction pattern comprising a peak at a diffraction angle (2?) of 28.6±0.2, and
a Raman spectrum comprising a Raman shift peak (cm-1) at 1292±2.

US Pat. No. 9,738,626

ANTAGONISTS OF PROSTAGLANDIN EP3 RECEPTOR

Pfizer Inc., New York, N...

1. A compound of Formula I:

wherein
m is 1 or 2;
n is 0, 1, or 2;
X and Y are nitrogen or CR2, provided that when X is nitrogen, Y is CR2 and further provided that when X is CR2, Y is nitrogen;

R1 is H, C1-6alkyl, or C3-6cycloalkyl;

R2 is H, halogen, C1-6alkyl, or C3-6cycloalkyl, wherein alkyl may be substituted with up to 3 halogens; and

Each R3 is independently halogen, C1-6alkyl, or C3-6cycloalkyl, wherein alkyl may be substituted with up to 3 halogens; or a pharmaceutically acceptable salt thereof, or a solvate
of said compound or salt thereof.

US Pat. No. 9,764,040

SPLICEOSTATIN ANALOGS AND METHODS FOR THEIR PREPARATION

Pfizer Inc., New York, N...

1. A compound of formula (II):
L-P  (II)
or a pharmaceutically acceptable salt thereof, wherein:
L is the linker moiety L1-L2-L3, where L3 is bound to P;

P is a radical of formula (I):

wherein:
a dashed line represents an optional bond;
each X1 is independently selected from the group consisting of: —O—, —S— and —NR—;

each X2 is independently selected from the group consisting of: —O—, —S— and —NR—;

each X? is CR or N;
each X? is CH—, CR—(C(R)2)m—NR—, CR—(C(R)2)m—O—; CR—(C(R)2)m—C(O)NR—, CR—(C(R)2)m—C(O)NR—NR—, CR—(C(R)2)m—SO2NR—, CR—(C(R)2)m—NR—NR—, CR—(C(R)2)m—NR—C(O)— or N— if X? binds to L2 or an additional L3, or otherwise is O, S, CRR, CR—(C(R)2)m—NRR or NRR;

each X?? is —(C(R)2)m—NR— or CR—(C(R)2)m—O— if X?? binds to L2, or otherwise is R;

Y is —C(R)2—, —O—, —NR— or —S—;

R1 is selected from the group consisting of: —R, —OR, —OCOR13, —OCONR14R15, —OCON(R14)NR(R15), ?O (double bond to oxygen) and —NR14R15;

R2 and R3 are independently selected from the group consisting of: hydrogen and C1-6alkyl;

R4 and R5 are independently selected from the group consisting of: hydrogen, —OR, —NR14R15 and oxo;

R6 and R7 are independently selected from the group consisting of: hydrogen, halogen, hydroxyl and C1-6alkyl optionally substituted with 1-3 substituents independently selected from hydroxyl and halogen,

R6 and R7, together with the carbon atom to which they are bound, form a C2-5alkylidene optionally substituted with 1-3 substituents independently selected from R,

R6 and R7 together are oxo, or

R6 and R7, together with the carbon atom to which they are bound, form a 3- to 5-membered heterocycloalkyl moiety comprising 1 or 2
heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, wherein said heterocycloalkyl
moiety may be optionally substituted with one to three substituents independently selected from R;

R8 is hydrogen, C1-6alkyl or —OR;

R9 is —(C(R)2)m—C(O)— or —(C(R)2)m—;

L1 is selected from: -acid, —NR-acid and


L2 is L2A-L2B-L2C or L2C-L2B-L2A where:

L2A comprises one or more components selected from:

—O—, —C(O)—, —C(O)NR—, —C(O)—C1-6alkyl-, —C(O)NRC1-6alkyl-, —C1-6alkyl(OCH2CH2)1-6—, —C(O)—C1-6alkyl-NRC(O)—, —C(O)—C1-6alkyl(OCH2CH2)1-6—, —C1-6alkyl(OCH2CH2)1-6—C(O)—, —C1-6alkyl-S—S—C1-6alkyl-NRC(O)CH2—, —C1-6alkyl-(OCH2CH2)1-6—NRC(O)CH2—, —C(O)—C1-6alkyl-NRC(O)C1-6alkyl-, —N?CR-phenyl-O—C1-6alkyl-, —N?CR-phenyl-O—C1-6alkyl-C(O)—, —C(O)—C1-6alkyl(OCH2CH2)1-6—NRC(O)—, —C(O)—C1-6alkyl-phenyl-(NR—C(O)—C1-6alkyl)1-4-, —C(O)—C1-6alkyl-(OCH2CH2)1-6—NRC(O)C1-6alkyl-, —C1-6alkyl-, —S—, —C(O)—C1-6alkyl-phenyl-NR—, —O—C1-6alkyl-S—, —C(O)—O—C1-6alkyl-S— and (—CH2—CH2—O—)1-20, or L2A is absent;

L2B is selected from AA0-aa, where AA is a natural or non-natural amino acid and aa is 12; and

L2C comprises one or more components selected from: —PABA- and —PABC—, or L2C is absent;

L3 is selected from one or more of: —C1-6alkyl-, —NR—C3-C8heterocyclyl-NR—, —NR—C3-C8carbocyclyl-NR—, —NR—C1-6alkyl-NR—, —NR—C1-6alkyl-, —S—, —NR—, —NR—NR— and —NR—C(O)—NR— where the two R groups optionally join to form a 4-10 membered ring, —NR—C1-6alkyl-phenyl-NR—, —NR—C1-6alkyl-phenyl-SO2—NR—, —SO2—, —NR—C1-6alkyl-phenyl-C(O)—,

or L3 is absent;
R13 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8carbocyclyl, C3-8heterocyclyl, C1-6alkyl-C6-14aryl, C1-6alkyl-C5-14heteroaryl, wherein R13 is optionally substituted with —NRR or —SO2NRR;

each R14 and R15 is independently selected from the group consisting of: hydrogen, hydroxyl, —NRR, —NRNR2, —C3-10carbocyclyl, —C1-6alkylene-C3-10carbocyclyl, —C3-10heterocyclyl, —C1-6alkylene-C3-10heterocyclyl, —(CH2CH2O)1-6CH2CH2C(O)OR, —(CH2CH2O)1-6CH2CH2NRR, —C1-6alkyl, C6-14aryl, —C1-6alkylene-C6-14aryl and —C5-14heteroaryl;

or R14 and R15, together with the atom or atoms to which they are joined, form a C3-10heterocyclyl ring,

wherein R14, R15, or both, or a ring formed with R14 and R15, are optionally substituted with —(C(R)2)m—R18 where each R18 is independently selected from (i) —NRR, (ii) —C(NRR)(C(O)OR), (iii) —S—R, (iv) aryl or heteroaryl optionally substituted
with one or more of halogen, —CF3, —(C(R)2)m—NRR or —(C(R)2)m—SO2NRR, (v) —SO2R, (vi) —S—S—C1-6alkyl-C(O)OR, (vii) —SO2NRR, (viii) —C(O)NRR, (ix) —C(O)OR, (x) —C4-6cycloalkyl optionally substituted with —NRR, —SO2NRR or —NR—C(O)(CH2)0-6NRR, (xi) —R, (xii) —OR, (xiii) —N(R)NRR, (xiv) —C(O)N(R)NRR, (xv) —(C(R)2)m—O—NRR and (xiv) —S—S—C1-6alkyl-NRR;

acid is an amino acid residue selected from —SCH2CH(COOH)(NH2), —NH(CH2)4CH(COOH)(NH2) and —C(O)(CH2)2CH(COOH)(NH2);

each R is independently selected from the group consisting of: hydrogen and —C1-6alkyl; and

each m is independently 0, 1, 2 or 3.
US Pat. No. 9,683,998

TUMOR NECROSIS FACTOR-LIKE LIGAND 1A SPECIFIC ANTIBODIES AND COMPOSITIONS AND USES THEREOF

Pfizer Inc., New York, N...

1. An isolated antibody or antigen-binding fragment thereof that specifically binds tumor necrosis factor-like ligand 1A (TL1A)
and comprises: (a) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:376,
a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 379, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
382; and (b) a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:110, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 111, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
112.