US Pat. No. 9,586,947

IMIDAZOLINE DERIVATIVES, PREPARATION METHODS THEREOF, AND THEIR APPLICATIONS IN MEDICINE

Shanghai Hengrui Pharmace...

1. A compound of formula (I), or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically
acceptable salt thereof:
wherein:
A is —CR?;
R? is hydrogen, halogen, or alkyl;
Z1 and Z2 are each independently alkyl;

R1 is S and R2 is O;

R3 is alkyl

substituted with one or more groups selected from the group consisting of halogen, cyano, amino, C3-6cycloalkyl, heterocyclyl, —OR6, —C(O)NR7R8, —S(O)mR6, —C(O)R6, —OC(O)R6, —NR7C(O)R8, —NR7C(O)OR8, and —C(O)OR6, wherein the C3-6, cycloalkyl and heterocyclyl are each optionally substituted with one or more groups selected from the group consisting of
halogen, cyano, amino, alkyl, haloalkyl, hydroxyalkyl, —OR6, —C(O)NR7R8, —S(O)mR6, —C(O)R6, —OC(O)R6, —NR7C(O)R8, —NR7C(O)OR8, and —C(O)OR6;

R4 and R5 are each independently selected from the group consisting of cyano, nitro, alkyl, haloalkyl, hydroxy, hydrogen, alkoxy, and
haloalkoxy;

R6 is hydrogen, alkyl, halogen, or alkoxy wherein the alkyl and alkoxy are each optionally substituted with one or more groups
selected from the group consisting of halogen, cyano, hydroxy, amino, oxo, alkyl, haloalkyl, hydroxyalkyl, and alkoxy;

R7 and R8 are each independently selected from the group consisting of hydrogen and alkyl, wherein the alkyl is optionally substituted
with one or more groups selected from the group consisting of halogen, cyano, hydroxy, amino, oxo, alkyl, haloalkyl, hydroxyalkyl,
and alkoxy; and

the heterocyclyl is a 3 to 6-membered ring having 1 to 2 oxygen atoms; and
m is 0, 1, or 2.

US Pat. No. 9,527,851

PYRROLE SIX-MEMBERED HETEROARYL RING DERIVATIVE, PREPARATION METHOD THEREOF, AND MEDICINAL USES THEREOF

Jiangsu Hengrui Medicine ...

18. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I), or a tautomer,
mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof according to
claim 1, and a pharmaceutically acceptable carrier.

US Pat. No. 9,458,219

HUMAN INSULIN ANALOGUE AND ACYLATED DERIVATIVE THEREOF

Shanghai Hengrui Pharmace...

1. A human insulin analogue or a physiologically acceptable salt thereof having an A chain and a B chain as follows:

wherein:
A0 is omitted;

A21 is N or G;

B3 is N;

B27 is T;

B28 is D;

B29 is K;

B30 is E;

B31 and B32 are omitted;

the ?-amino group of the lysine residue at B29 is optionally acylated; and
optionally, the ?-amino group at the N-terminus of the A chain or B chain is acylated.

US Pat. No. 10,087,191

PIPERIDINE DERIVATIVE AND PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF

Jiangsu Hengrui Medicine ...

1. A compound of formula (I):or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof,wherein:ring A is selected from the group consisting of:

R is selected from the group consisting of hydrogen, alkyl and cycloalkyl, wherein the alkyl and cycloalkyl are each optionally substituted by one or more groups selected from the group consisting of halogen, amino, cyano, hydroxy, alkoxy, carboxy, cycloalkyl, aryl and heteroaryl;
each R1 is identical or different and each is independently selected from the group consisting of hydrogen, alkyl, halogen, cyano and alkoxy, wherein the alkyl and alkoxy are each optionally substituted by one or more groups selected from the group consisting of halogen, amino, cyano and hydroxy;
R2 is selected from the group consisting of alkyl, haloalkyl and cycloalkyl, wherein the alkyl and cycloalkyl are each optionally substituted by one or more groups selected from the group consisting of halogen, amino, cyano, hydroxy, alkoxy, carboxy, cycloalkyl, aryl and heteroaryl;
R3 is selected from the group consisting of hydrogen, alkyl and cycloalkyl, wherein the alkyl and cycloalkyl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, amino, cyano, hydroxy, alkoxy, carboxy and cycloalkyl;
each R4 is identical or different and each is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkoxy, amino, halogen, cyano, carboxy, alkenyl, alkynyl, heterocyclyl, aryl, heteroaryl, —OR5, —NHC(O)OR5 and —NHC(O)NR6R7, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of Rc, alkyl, haloalkyl, hydroxyalkyl, halogen, amino, nitro, cyano, hydroxy, oxo, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl;
Rc is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxy, amino, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxy, amino, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl and —C(O)NR6R7;
R6 and R7 are identical or different and each is independently selected from the group consisting of hydrogen, alkyl, hydroxy, halogen, cyano, amino, nitro, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxy, amino, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
Ra and Rb are identical or different and each is independently selected from the group consisting of hydrogen, alkyl, hydroxy, halogen, cyano, amino, nitro, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxy, amino, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, —OR5, aryl and heteroaryl;
m is 0, 1, 2, 3 or 4; and
n is 0, 1, 2, 3 or 4.

US Pat. No. 9,637,484

CYCLOALKYL ACID DERIVATIVE, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL APPLICATION THEREOF

SHANGHAI HENGRUI PHARMACE...

1. A compound of formula (I), or a tautomer, mesomer, racemate, enantiomer, or diastereomer thereof, or mixture thereof, or
a pharmaceutically acceptable salt thereof:
wherein:
ring A is cycloalkyl;
W1 is N;

W2 is CRb, wherein Rb is selected from the group consisting of hydrogen and alkyl;

W3 is CRc;

Rc is selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl,
aryl, heteroaryl, —OR4, —S(O)mR4, —C(O)R4, —C(O)OR4, —C(O)NR5R6, —NR5R6 and —NR5C(O)R6, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted
with one or more groups selected from the group consisting of halogen, cyano, nitro, oxo, alkyl, haloalkyl, hydroxyalkyl,
alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR4, —S(O)mR4, —C(O)R4, —C(O)OR4, —C(O)NR5R6, —NR5R6 and —NR5C(O)R6;

R1 is hydrogen or alkyl;

R2 and R3 are each independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, haloalkyl and hydroxyalkyl;

R4 is selected from the group consisting of hydrogen, alkyl, halogen, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein
the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted with one or more groups
selected from the group consisting of halogen, cyano, nitro, hydroxy, oxo, alkyl, haloalkyl, hydroxyalkyl, alkoxy, cycloalkyl,
heterocyclyl, aryl, heteroaryl, carboxyl, alkoxycarbonyl, —C(O)NR5R6, —NR5R6 and —NR5C(O)R6;

R5 and R6 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
and

m is 0, 1, or 2.

US Pat. No. 10,064,848

PYRIDIC KETONE DERIVATIVES, METHOD OF PREPARING SAME, AND PHARMACEUTICAL APPLICATION THEREOF

Shanghai Hengrui Pharmace...

1. A compound of formula (IA), or a pharmaceutically acceptable salt thereof:wherein:R1 is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently and optionally substituted with one or more groups selected from the group consisting of halogen, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR7, —C(O)OR7, —OC(O)R7, —O(CH2)nC(O)OR7, —C(O)R7, —C(O)NHR7, —NHC(O)R7, —NHC(O)OR7, —NHS(O)mR7, —NR8R9, —OC(O)NR8R9, and —C(O)NR8R9;
R4 is selected from the group consisting of aryl and heteroaryl, wherein the aryl and heteroaryl are each independently and optionally substituted with one or more groups selected from the group consisting of halogen, cyano, hydroxy, nitro, alkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, heterocyclyl, aryl, heteroaryl, —OR7, —C(O)OR7, —OC(O)R7, —O(CH2)nC(O)OR7, —C(O)R7, —NHC(O)R7, —NHC(O)OR7, —NHS(O)mR7, —NR8R9, —OC(O)NR8R9, and —C(O)NR8R9;
R5 is selected from the group consisting of hydrogen, alkyl, alkenyl, and alkynyl, wherein the alkyl, alkenyl, and alkynyl are each independently and optionally substituted with one or more groups selected from the group consisting of halogen, hydroxy, alkoxy, cyano, and haloalkyl;
R6 is selected from the group consisting of hydrogen, halogen and alkyl, wherein the alkyl is optionally substituted with one or more groups selected from the group consisting of halogen, hydroxy, cyano, nitro, alkoxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
PG is selected from the group consisting of alkyl and an amino-protecting group, wherein the alkyl and benzyl are each optionally substituted with one or more groups selected from the group consisting of halogen, cyano, nitro, alkyl, cycloalkyl, heterocyclyl, heteroaryl, and —OR7; and
R7 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted with one or more groups selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxyl, and alkoxycarbonyl.

US Pat. No. 9,139,548

POLYCYCLIC DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF

Jiangsu Hengrui Medicine ...

1. A compound of formula (I), or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically
acceptable salt thereof:
wherein:
A is selected from the group consisting of —O—, —CH2—, and —CH2CH2—;

L is selected from the group consisting of —O— and —NH—;
ring B is selected from the group consisting of aryl and heteroaryl;
R1, R2, and R3 are each independently selected from the group consisting of halogen, hydroxyl, cyano, nitro, alkyl, alkoxy, cycloalkyl, heterocyclyl,
aryl, heteroaryl, —C(O)OR5, —OC(O)R5, —C(O)R5, —NHC(O)R5, —NR6R7, and —S(O)mR5, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, or heteroaryl is each optionally substituted with one or more
groups selected from the group consisting of halogen, hydroxyl, cyano, nitro, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl,
heteroaryl, —C(O)OR5, —OC(O)R5, —C(O)R5, —NHC(O)R5, —NR6R7, and —S(O)mR5;

R4 is selected from the group consisting of the following cycloalkyl, heterocyclyl, and heteroaryl:


wherein the cycloalkyl, heterocyclyl, or heteroaryl is each optionally substituted with one or more groups selected from the
group consisting of halogen, hydroxyl, cyano, nitro, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)OR5, —OC(O)R5, —C(O)R5, —NHC(O)R5, —NR6R7, and —S(O)mR5;

R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl,
cycloalkyl, heterocyclyl, aryl, or heteroaryl is each optionally substituted with one or more groups selected from the group
consisting of alkyl, halogen, hydroxyl, cyano, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxyl, and alkoxycarbonyl;

R6 and R7 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl,
wherein the alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is each optionally substituted with one or more groups selected
from the group consisting of alkyl, halogen, hydroxyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxyl, and alkoxycarbonyl;

m is 0, 1, or 2;
n is 0, 1, 2, or 3;
p is 0, 1, 2, 3, or 4; and
q is 0, 1, 2, 3, or 4.

US Pat. No. 9,120,762

SALTS OF BICYCLO-SUBSTITUTED PYRAZOLON AZO DERIVATIVES, PREPARATION METHOD AND USE THEREOF

Jiangsu Hengrui Medicine ...

1. A method for the treatment of thrombocytopenia comprising administering to a subject in need thereof a therapeutically
effective amount of a pharmaceutically acceptable salt of the compound having formula (I):

wherein:
Het is selected from the group consisting of furyl and thienyl;
R1, R2, R3 and R4 are each independently selected from the group consisting of hydrogen and alkyl;

n is 0, 1 or 2;
wherein the pharmaceutically acceptable salt is a base addition salt selected from the group consisting of sodium salt, lithium
salt, potassium salt, calcium salt, magnesium salt, arginine salt, lysine salt, methanamine salt, dimethylamine salt, trimethylamine
salt, ethylamine salt, diethylamine salt, triethylamine salt, ethanolamine salt, piperazine salt, dibenzyl ethylenediamine
salt, meglumine salt, tromethamine salt, tetramethyl quaternary ammonium salt, tetraethyl quaternary ammonium salt, choline
salt, and combinations thereof.

US Pat. No. 9,358,227

PHARMACEUTICAL USES OF 6-AMINO QUINAZOLINE OR 3-CYANO QUINOLINE DERIVATIVES

Jiangsu Hengrui Medicine ...

1. A method of treating a cancer selected from the group consisting of stomach cancer and non-small cell lung cancer in a
subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition
comprising a pharmaceutically acceptable carrier and a compound of formula (I), or a tautomer, racemate, enantiomer, diastereoisomer
or mixture thereof, or a pharmaceutically acceptable salt thereof:

wherein:
A is carbon atom,
R1 is selected from the group consisting of hydrogen and alkoxyl; wherein said alkoxyl is optionally substituted with one or
more groups selected from the group consisting of halogen and alkoxyl;

R2 is cyano;

R3 is a radical having the following formula:


wherein:
D is selected from the group consisting of aryl and heteroaryl, wherein said aryl or heteroaryl is each independently optionally
substituted with one or more groups selected from the group consisting of halogen, alkyl and trifluoromethyl;

T is selected from the group consisting of —(CH2)r-, —O(CH2)r-, —NH(CH2)r- and —S(O)r(CH2)r-; and

L is selected from the group consisting of aryl and heteroaryl, wherein said aryl or heteroaryl is each independently optionally
substituted with one or more groups selected from the group consisting of halogen and alkyl;

R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, alkoxyl, hydroxyl, hydroxyalkyl, halogen, carbonyl,
amino, cyano, nitro, carboxyl and carboxylic ester;

B is selected from the group consisting of carbon atom, oxygen atom and S(O)r;
when B is carbon atom, R6 and R7 are each independently selected from the group consisting of hydrogen, alkyl, alkoxyl, hydroxyl, hydroxyalkyl, halogen, carbonyl,
amino, cyano, nitro, carboxyl and carboxylic ester;

when B is oxygen atom or S(O)r, R6 and R7 are absent;

R8 is selected from the group consisting of hydrogen and alkyl;

R9 is selected from the group consisting of hydrogen, alkyl, aryl, carboxyl and carboxylic ester;

r is 0, 1, or 2; and
n is 1, 2, 3, 4, or 5.
US Pat. No. 9,862,765

IL-17A BINDING AGENT AND USES THEREOF

Shanghai Hengrui Pharmace...

1. An IL-17A binding agent comprising an antibody to IL-17A or an antigen-binding fragment thereof, wherein the antibody comprises:
an antibody light chain variable region comprising 3 light chain complementarity determining (LCDR) regions having the amino
acid sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; and an antibody heavy chain variable region
comprising 3 heavy chain complementarity determining (HCDR) regions having the amino acid sequences of SEQ ID NO: 10, SEQ
ID NO: 11, and SEQ ID NO: 12, respectively.

US Pat. No. 9,408,915

TOLVAPTAN SOLID DISPERSION AND ITS PREPARATION METHOD

Jiangsu Hengrui Medicine ...

1. A pharmaceutical amorphous solid dispersion, comprising amorphous tolvaptan or a salt thereof as an active ingredient,
a carrier comprising cross-linked polyvinylpyrrolidone, and one or more water soluble polymers, wherein the one or more water
soluble polymers are selected from the group consisting of polyvinylpyrrolidone, hydroxypropylmethyl cellulose, hydroxyethylcellulose
and methylcellulose, wherein the amorphous tolvaptan or salt thereof, the cross-linked polyvinylpyrrolidone, and the one or
more water soluble polymers are at a ratio of 2:1:0.1 by weight.

US Pat. No. 10,022,365

LIPOSOME OF IRINOTECAN OR IRINOTECAN HYDROCHLORIDE AND PREPARATION METHOD THEREOF

Jiangsu Hengrui Medicine ...

1. A liposome, comprising:irinotecan hydrochloride,
hydrogenated soybean phosphatidylcholine,
polyethylene glycol 2000-distearoyl phosphatidyl ethanolamine,
cholesterol, and
ethylene diamine tetraacetic acid disodium,
wherein the weight ratio of the cholesterol to the hydrogenated soybean phosphatidylcholine is about 1:4, and
there is no significant change in the particle size and encapsulation efficiency of the liposome after the liposome is stored at 25° C. for 60 days.

US Pat. No. 10,005,781

PYRAZOLOPYRIMIDONE OR PYRROLOTRIAZONE DERIVATIVES, METHOD OF PREPARING SAME, AND PHARMACEUTICAL APPLICATIONS THEREOF

Shanghai Hengrui Pharmace...

1. A compound of formula (II), or a tautomer, mesomer, racemate, enantiomer, or diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof:
wherein:
R1 is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, and —OR6, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each independently and optionally further substituted with one or more groups selected from the group consisting of halogen, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR6, —C(O)OR6, —OC(O)R6, —NHS(O)mR6, —C(O)R6, —NHC(O)R6, —NHC(O)OR6, —NR7R8, —OC(O)NR7R8, —C(O)NR7R8, —NHC(O)NHR6, and —NHC(O)NHOR6;
R2 is alkyl, wherein the alkyl is further substituted with one or more groups selected from the group consisting of aryl and heteroaryl, wherein the aryl and heteroaryl are each optionally further substituted with one or more groups selected from the group consisting of halogen, alkyl, haloalkyl, cyano, nitro, —C(O)OR6, —C(O)NR7R8, —OC(O)NR7R8, —OR6, —NHS(O)mR6, —NHC(O)R6, and —NR7R8;
R3 is selected from the group consisting of aryl and heteroaryl, wherein the aryl and heteroaryl are each optionally further substituted with one or more groups selected from the group consisting of halogen, alkyl, haloalkyl, —OR6, —C(O)OR6, —OC(O)R6, —C(O)R6, —NR7R8, —OC(O)NR7R8, —C(O)NR7R8, —NHS(O)mR6, —NHC(O)R6, —NHC(O)OR6, —NHC(O)NHR6, and —NHC(O)NHOR6;
R4 is alkyl;
R5 is selected from the group consisting of hydrogen, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR5, —NR7R8, and —NR7S(O)mR6, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally further substituted with one or more groups selected from the group consisting of halogen, oxo, alkyl, haloalkyl, hydroxyalkyl, —OR6, —C(O)OR6, —OC(O)R6, —NR7S(O)mR6, —S(O)mR6, —C(O)R6, and —NHC(O)R6;
R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each independently and optionally further substituted with one or more groups selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid, and carboxylic ester;
R7 and R8 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each independently and optionally further substituted with one or more groups selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid, and carboxylic ester;
or, R7 and R8 are taken together with the attached N atom to form a heterocyclyl, wherein the heterocyclyl contains one or more heteroatoms selected from the group consisting of N, O, and S(O)m, and the heterocyclyl is optionally further substituted with one or more groups selected from the group consisting of alkyl, halogen, hydroxyl, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid, and carboxylic ester;
m is 0, 1, or 2;
n is 1, 2, 3, or 4; and
p is 0, 1, or 2.

US Pat. No. 9,283,189

SUSTAINED-RELEASE PREPARATION OF IVABRADINE OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF

Jiangsu Hengrui Medicine ...

1. A sustained release preparation of ivabradine or a pharmaceutically acceptable salt thereof, comprising ivabradine or the
pharmaceutically acceptable salt thereof and sustained release skeleton materials, wherein the sustained release skeleton
materials are one or more selected from the group consisting of polyoxyethylene and a mixture of polyvinyl acetate and polyvinylpyrrolidone,
such that the sustained release preparation prolongs in vivo retention time of ivabradine for up to at least about twelve
hours, and wherein the sustained release preparation is prepared by a process comprising a direct compression tabletting process
or granulation tabletting process.

US Pat. No. 9,914,703

PYRIDIC KETONE DERIVATIVES, METHOD OF PREPARING SAME, AND PHARMACEUTICAL APPLICATION THEREOF

Shanghai Hengrui Pharmace...

1. A compound of formula (I), or a tautomer, mesomer, racemate, enantiomer, or diastereomer thereof, or mixture thereof, or
a pharmaceutically acceptable salt thereof:
wherein:
R1 is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the cycloalkyl, heterocyclyl,
aryl and heteroaryl are each independently and optionally substituted with one or more groups selected from the group consisting
of halogen, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR7, —C(O)OR7, —OC(O)R7, —O(CH2)nC(O)OR7, —C(O)R7, —C(O)NHR7, —NHC(O)R7, —NHC(O)OR7, —NHS(O)mR7, —NR8R9, —OC(O)NR8R9, and —C(O)NR8R9;

R2 and R3 are each independently selected from the group consisting of hydrogen and alkyl, wherein the alkyl is optionally substituted
with one or more groups selected from the group consisting of halogen, cyano, nitro, alkenyl, alkynyl, heterocyclyl, aryl,
heteroaryl, —OR7, —C(O)OR7, —OC(O)R7, —O(CH2)nC(O)OR7, —C(O)R7, —NHC(O)R7, —NHC(O)OR7, —NHS(O)mR7, —NR8R9, —OC(O)NR8R9, and —C(O)NR8R9;

R4 is selected from the group consisting of aryl and heteroaryl, wherein the aryl and heteroaryl are each independently and optionally
substituted with one or more groups selected from the group consisting of halogen, cyano, hydroxy, nitro, alkyl, haloalkyl,
hydroxyalkyl, alkenyl, alkynyl, heterocyclyl, aryl, heteroaryl, —OR7, —C(O)OR7, —OC(O)R7, —O(CH2)nC(O)OR7, —C(O)R7, —NHC(O)R7, —NHC(O)OR7, —NHS(O)mR7, —NR8R9, —OC(O)NR8R9, and —C(O)NR8R9;

R5 is selected from the group consisting of hydrogen, alkyl, alkenyl, and alkynyl, wherein the alkyl, alkenyl, and alkynyl are
each independently and optionally substituted with one or more groups selected from the group consisting of halogen, hydroxy,
alkoxy, cyano, and haloalkyl;

R6 is selected from the group consisting of hydrogen, halogen and alkyl, wherein the alkyl is optionally substituted with one
or more groups selected from the group consisting of halogen, hydroxy, cyano, nitro, alkoxy, cycloalkyl, heterocyclyl, aryl,
and heteroaryl;

R7 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl,
cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently and optionally substituted with one or more groups selected
from the group consisting of alkyl, halogen, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxyl, and alkoxycarbonyl;

R8 and R9 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl,
wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each independently and optionally substituted with one
or more groups selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl,
carboxyl, and alkoxycarbonyl; or

alternatively, R8 and R9 together with the nitrogen atom to which they are attached form a heterocyclyl, wherein the heterocyclyl contains one or more
heteroatoms selected from the group consisting of N, O, and S(O)m, and the heterocyclyl is optionally substituted with one or more groups selected from the group consisting of alkyl, halogen,
hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxyl, and alkoxycarbonyl;

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

US Pat. No. 10,081,629

AMIDE DERIVATIVES AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PREPARATION METHOD THEREOF AND MEDICINAL APPLICATION THEREOF

Jiangsu Hengrui Medicine ...

1. A compound of formula (III), formula (IV), or formula (V), or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or pharmaceutically acceptable salt thereof:wherein:X is —CH— or N;
each of E, G and W is independently selected from the group consisting of CRa, NRb, and N;
Ra and Rb are each independently selected from the group consisting of hydrogen, halogen, alkoxy, cyano, nitro, alkyl, cycloalkyl, heterocyclyl, —C(O)OR5, —OC(O)R5, —NHS(O)mR5, —C(O)R5, —NHC(O)R5, —NHC(O)OR5, —NR6R7, —OC(O)NR6R7 and —C(O)NR6R7, wherein the alkyl, cycloalkyl and heterocyclyl are each optionally further substituted by one or more groups selected from the group consisting of halogen, hydroxy, alkoxy, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)OR5, —OC(O)R5, —NHS(O)mR5, —C(O)R5, —NHC(O)R5, —NHC(O)OR5, —NR6R7, —OC(O)NR6R7 and —C(O)NR6R7;
each of A, B and Y is —CH—;
R1 is selected from the group consisting of alkyl and cycloalkyl, wherein the alkyl or cycloalkyl is optionally further substituted by one or more groups selected from the group consisting of alkyl, halogen and haloalkyl;
R2 is selected from the group consisting of halogen and haloalkyl;
R4 is selected from the group consisting of aryl and heteroaryl, wherein the aryl and heteroaryl are each optionally further substituted by one or more groups selected from the group consisting of halogen, alkoxy, hydroxyl, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)OR5, —OC(O)R5, —NHS(O)mR5, —C(O)R5, —NHC(O)R5, —NHC(O)OR5, —NR6R7, —OC(O)NR6R7 and —C(O)NR6R7;
R5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, aryl and heteroaryl are each optionally further substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxyl, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid and carboxylate group;
R6 and R7 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently and optionally further substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxyl, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid and carboxylate group; or
R6 and R7 are taken together with the nitrogen atom to which they are attached to form a heterocyclyl, wherein the heterocyclyl optionally contains one or more heteroatoms selected from the group consisting of N, O and S (O)m, and wherein the heterocyclyl is optionally further substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxyl, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid and carboxylate group;
m is 0, 1 or 2; and
t is 0 or 1.

US Pat. No. 9,359,366

INTERMEDIATE OF TICAGRELOR AND PREPARATION METHOD THEREFOR, AND PREPARATION METHOD FOR TICAGRELOR

Jiangsu Hengrui Medicine ...

1. A compound of Formula (VI):

wherein R is hydrogen or a hydroxyl protecting group.

US Pat. No. 10,030,018

HYDROXYETHYL SULFONATE OF CYCLIN-DEPENDENT PROTEIN KINASE INHIBITOR, CRYSTALLINE FORM THEREOF AND PREPARATION METHOD THEREFOR

Jiangsu Hengrui Medicine ...

1. Crystal form I of a compound of formula (I):
wherein the crystal has a characteristic X-ray powder diffraction spectrum comprising diffraction peaks at diffraction angles (2?) of about 4.17, 8.26, 9.04, 10.78, 12.38, 14.01, 18.50, 18.89, 20.69, 21.58, 23.87 and 28.15.
US Pat. No. 9,309,226

CRYSTALLINE FORM I OF TYROSINE KINASE INHIBITOR DIMALEATE AND PREPARATION METHODS THEREOF

Jiangsu Hengrui Medicine ...

1. A form I crystal of (R,E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)-phenylamino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(1-methylpyrrolidin-2-yl)
acrylamide dimaleate, wherein using Cu—K? radiation to obtain an X-ray diffraction pattern represented by 2? angle (interplanar
crystal spacing), the form I crystal has the X-ray diffraction pattern comprising characteristic peaks at 6.28 (14.06), 6.74
(13.10), 10.60 (8.34), 11.58 (7.64), 13.50 (6.55), 14.90 (5.94), 15.80 (5.60), 18.26 (4.85), 20.66 (4.30), 21.14 (4.20), 22.96
(3.87), 24.34 (3.65), 25.54 (3.49), and 26.12 (3.41).

US Pat. No. 9,422,300

BISULFATE OF JANUS KINASE (JAK) INHIBITOR AND PREPARATION METHOD THEREFOR

Jiangsu Hengrui Medicine ...

1. (3aR,5s,6aS)—N-(3-methoxyl-1,2,4-thiadiazol-5-yl)-5-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide
bisulfate of formula (I)

US Pat. No. 9,895,355

METHODS OF TREATING ANDROGEN RECEPTOR-MEDIATED DISORDERS WITH IMIDAZOLINE DERIVATIVES

Shanghai Hengru Pharmaceu...

1. A method for treating breast cancer, the method comprising administering to a subject in need thereof a therapeutically
effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula
(I), or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt
thereof:
wherein:
A is —CR?;
R? is hydrogen, halogen, or alkyl;
Z1 and Z2 are each independently alkyl;

R1 is S and R2 is O;

R3 is alkyl, wherein the alkyl is substituted with one or more groups selected from the group consisting of halogen, cyano, amino,
C3-6 cycloalkyl, heterocyclyl, —OR6, —C(O)NR7R8, —S(O)mR6, —C(O)R6, —OC(O)R6, —NR7C(O)R8, —NR7C(O)OR8, and —C(O)OR6, wherein the C3-6 cycloalkyl and heterocyclyl are each optionally substituted with one or more groups selected from the group consisting of
halogen, cyano, amino, alkyl, haloalkyl, hydroxyalkyl, -OR6, —C(O)NR7R8, —S(O)mR6, —C(O)R6, —OC(O)R6, —NR7C(O)R8, —NR7C(O)OR8, and —C(O)OR6;

R4 and R5 are each independently selected from the group consisting of cyano, nitro, alkyl, haloalkyl, hydroxy, hydrogen, alkoxy, and
haloalkoxy;

R6 is hydrogen, alkyl, halogen, or alkoxy wherein the alkyl and alkoxy are each optionally substituted with one or more groups
selected from the group consisting of halogen, cyano, hydroxy, amino, oxo, alkyl, haloalkyl, hydroxyalkyl, and alkoxy;

R7 and R8 are each independently selected from the group consisting of hydrogen and alkyl, wherein the alkyl is optionally substituted
with one or more groups selected from the group consisting of halogen, cyano, hydroxy, amino, oxo, alkyl, haloalkyl, hydroxyalkyl,
and alkoxy;

the heterocyclyl is a 3 to 6 membered ring having 1 to 2 oxygen atoms; and
m is 0, 1, or 2.
US Pat. No. 10,206,980

IL-15 HETERODIMERIC PROTEIN AND USES THEREOF

Shanghai Hengrui Pharmace...

1. An IL-15 heterodimeric protein, comprising:protein (I) and protein (H);
wherein protein (I) is recombinantly produced and comprises the sequence of IL-15 and the sequence of a first Fc variant;
protein (H) is a second Fc variant, or is recombinantly produced and comprises the sequence of IL-15R? or a variant thereof and the sequence of a second Fc variant, wherein the IL-15R? variant is an extracellular domain of IL-15R? or a functional fragment thereof, the functional fragment being a C-terminal truncated form of the extracellular domain of IL-15R? having the activity of IL-15R?; and
protein (I) and protein (H) form a stable heterodimeric protein by an interaction between the first Fc variant and the second Fc variant.

US Pat. No. 9,951,077

AMINOPYRIDAZINONE COMPOUNDS AS PROTEIN KINASE INHIBITORS

Jiangsu Hengrui Medicine ...

1. A compound, a tautomer, a pharmaceutically acceptable salt, a solvate, or a hydrate thereof, wherein the compound is selected from the group consisting of:

US Pat. No. 10,344,034

PYRAZOLOPYRIMIDONE OR PYRROLOTRIAZONE DERIVATIVES, METHOD OF PREPARING SAME, AND PHARMACEUTICAL APPLICATIONS THEREOF

Shanghai Hengrui Pharmace...

1. A process for preparing the compound of formula (II), or a tautomer, mesomer, racemate, enantiomer, or diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof:
the process comprising:
(a) reacting a compound of formula (IA) with an amine of formula NH(R4)(CH2)nR; and optionally reducing and/or acylating the resulting product to obtain the compound of formula (II); or
(b) reacting a compound of formula (IB) with R2X in the presence of an alkaline reagent; and optionally reducing and/or acylating the resulting product to obtain the compound of formula (II):

wherein:
X is halogen;
G is C;
D and E are each N;
R1 is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, and —OR6, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each independently and optionally further substituted with one or more groups selected from the group consisting of halogen, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR6, —C(O)OR6, —OC(O)R6, —NHS(O)mR6, —C(O)R6, —NHC(O)R6, —NHC(O)OR6, —NR7R8, —OC(O)NR7R8, —C(O)NR7R8, —NHC(O)NHR6, and —NHC(O)NHOR6;
R2 is alkyl, wherein the alkyl is further substituted with one or more groups selected from the group consisting of aryl and heteroaryl, wherein the aryl and heteroaryl are each optionally further substituted with one or more groups selected from the group consisting of halogen, alkyl, haloalkyl, cyano, nitro, —C(O)OR6, —C(O)NR7R8, —OC(O)NR7R8, —OR6, —NHS(O)mR6, —NHC(O)R6, and —NR7R8;
R3 is selected from the group consisting of aryl and heteroaryl, wherein the aryl and heteroaryl are each optionally further substituted with one or more groups selected from the group consisting of halogen, alkyl, haloalkyl, —OR6, —C(O)OR6, —OC(O)R6, —C(O)R6, —NR7R8, —OC(O)NR7R8, —C(O)NR7R8, —NHS(O)mR6, —NHC(O)R6, —NHC(O)OR6, —NHC(O)NHR6, and —NHC(O)NHOR6;
R4 is alkyl;
R5 is selected from the group consisting of hydrogen, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR5, —NR7R8, and —NR7S(O)mR6, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally further substituted with one or more groups selected from the group consisting of halogen, oxo, alkyl, haloalkyl, hydroxyalkyl, —OR6, —C(O)OR6, —OC(O)R6, —NR7S(O)mR6, —S(O)mR6, —C(O)R6, and —NHC(O)R6;
R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each independently and optionally further substituted with one or more groups selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid, and carboxylic ester;
R7 and R8 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each independently and optionally further substituted with one or more groups selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid, and carboxylic ester;
or, R7 and R8 are taken together with the attached N atom to form a heterocyclyl, wherein the heterocyclyl contains one or more heteroatoms selected from the group consisting of N, O, and S(O)m, and the heterocyclyl is optionally further substituted with one or more groups selected from the group consisting of alkyl, halogen, hydroxyl, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid, and carboxylic ester;
m is 0, 1, or 2;
n is 1, 2, 3, or 4; and
p is 0, 1, or 2.

US Pat. No. 10,160,759

HYDROXYETHYL SULFONATE OF CYCLIN-DEPENDENT PROTEIN KINASE INHIBITOR, CRYSTALLINE FORM THEREOF AND PREPARATION METHOD THEREFOR

Jiangsu Hengrui Medicine ...

1. A compound of formula (I):
US Pat. No. 10,150,770

CRYSTAL FORM OF BISULFATE OF JAK INHIBITOR AND PREPARATION METHOD THEREFOR

Jiangsu Hengrui Medicine ...

1. Crystal form I of (3aR,5s,6aS)—N-(3-methoxyl-1,2,4-thiadiazole-5-yl)-5-(methyl(7H-pyrrolo[2,3-d]pyrimidine-4-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-formamide bisulfate, wherein the crystal has a characteristic X-ray powder diffraction (XRPD) spectrum comprising diffraction peaks at angles (2?) of about 17.84, 18.81, and 24.12.

US Pat. No. 10,144,737

SUBSTITUTED ETHYNYL HETEROBICYCLIC COMPOUNDS AS TYROSINE KINASE INHIBITORS

JIANGSU HENGRUI MEDICINE ...

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof,wherein Z is selected from the group consisting of —(CH2)m—, —O(CH2)m—, and —(CH2)mO(CH2)m—; and where m is an integer from 1-3;W is CH or N;
R is a cyclic group selected from the group consisting of phenyl, naphthalenyl, benzodioxolyl, benzofuranyl, benzothiophenyl, thiophenyl, quinolinyl, cyclohexyl, furanyl, pyrazolyl, tetrahydropyranyl, and indazolyl, wherein R is either unsubstituted or substituted with one or more of R3, R4 and R5;
R1 and R2 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, C3-C8 cycloalkyl, C3-C8 cycloheteroalkyl, aryl, and heteroaryl; or R1 and R2 may combine with an atom or atoms to which they are attached to form 3- to 12-membered heterocyclic, C6-12 aryl, or 5- to 12-membered heteroaryl, wherein R1 and R2 are independently either unsubstituted or substituted with a substituent selected from the group consisting of —C(O)CH?CH2, —C(O)CH?CHCH2N(CH3)2, —C(O)CH?CHCH2NH(CH3), —C(O)CH?CHCH3,

provided that at least one of R1 and R2 is not hydrogen; and
R3, R4 and R5 are each independently selected from the group consisting of H, halogen, —CN, —CF3, —OCF3, —OR9, alkyl;
wherein R9 is alkyl.

US Pat. No. 10,364,234

PYRIDINECARBOXAMIDE DERIVATIVES, PREPARATION METHOD THEREOF AND PHARMACEUTICAL USES THEREOF

Jiangsu Hengrui Medicine ...

1. A compound of formula (II),
or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or pharmaceutically acceptable salt thereof,
wherein
R1 is alkyl, wherein the alkyl is optionally further substituted by one or more groups selected from the group consisting of halogen, hydroxyl, alkoxy, cycloalkyl, aryl, and carboxyl;
R2 is hydrogen;
R4 is selected from the group consisting of hydrogen, alkyl, halogen, cyano, nitro, alkoxy, cycloalkyl, and aryl;
and
n is 2.

US Pat. No. 10,301,344

L-PROLINE COMPLEX OF SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITOR, MONOHYDRATE AND CRYSTAL FORM THEREOF

Jiangsu Hengrui Medicine ...

1. Crystal form A of a complex of formula (I):
wherein the crystal is a crystal of a monohydrate, and the crystal is characterized by an X-ray powder diffraction (XRPD) spectrum comprising diffraction peaks at angles (2?) of about 7.82, 17.28, and 18.89.

US Pat. No. 10,118,911

P-TOLUENESULFONATE FOR MEK KINASE INHIBITOR, AND CRYSTAL FORM THEREOF AND PREPARATION METHOD THEREFOR

Jiangsu Hengrui Medicine ...

1. A crystal form I of 2-((2-fluoro-4-iodophenyl)amino)-1-methyl-4-((6-methylpyridin-3-yl)oxy)-6-oxo-1,6-dihydropyridine-3-carboxamide p-toluenesulfonate of formula (I),
wherein the crystal has a characteristic X-ray powder diffraction spectrum comprising diffraction peaks at diffraction angles (2?) of about 10.18, 17.13, 17.59, 21.51, and 21.88.

US Pat. No. 10,442,793

OXA SPIRO DERIVATIVE, PREPARATION METHOD THEREFOR, AND APPLICATIONS THEREOF IN MEDICINES

Jiangsu Hengrui Medicine ...

1. A compound of formula (I):
or a tautomer, mesomer, racemate, enantiomer, diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof,
wherein:
ring A is selected from the group consisting of cycloalkyl and heterocyclyl;
R is selected from the group consisting of aryl and heteroaryl, wherein the aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, haloalkyl, halogen, amino, nitro, cyano, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR3, —C(O)R3, —C(O)OR3, —S(O)mR3 and —NR4R5;
each R1 is identical or different and each is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, halogen, amino, nitro, hydroxy, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR3, —C(O)R3, —C(O)OR3, —S(O)mR3 and —NR4R5, wherein the alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, haloalkyl, halogen, amino, nitro, cyano, hydroxy, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
each R2 is identical or different and each is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, halogen, amino, nitro, hydroxy, cyano, oxo, alkenyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR3, —C(O)R3, —C(O)OR3, —S(O)mR3 and —NR4R5, wherein the alkyl, alkoxy, alkenyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of deuterium, alkyl, haloalkyl, halogen, amino, nitro, cyano, hydroxy, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
or two R2 are taken together to form a cycloalkyl or heterocyclyl, wherein the cycloalkyl or heterocyclyl is each optionally substituted by one or more groups selected from the group consisting of alkyl, haloalkyl, halogen, amino, nitro, cyano, hydroxy, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R3 is selected from the group consisting of hydrogen, alkyl, deuterated alkyl, amino, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxy, amino, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, hydroxyalkyl, hydroxy, amino, alkoxycarbonyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxy, amino, alkoxycarbonyl, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
p and q are each independently 0, 1, 2, 3 or 4; and
m is 0, 1 or 2.

US Pat. No. 10,442,794

PROCESSES FOR PREPARING PYRIDINE CARBOXAMIDE DERIVATIVES

Jiangsu Hengrui Medicine ...

1. A process for preparing a compound of formula (II), or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or pharmaceutically acceptable salt thereof, the process comprising heating a compound of formula (IA) with a substituted benzofuran derivative (IB):
wherein:
R1 is alkyl, wherein the alkyl is optionally further substituted by one or more groups selected from the group consisting of halogen, hydroxyl, alkoxy, cycloalkyl, aryl, and carboxyl;
R2 is hydrogen;
R4 is selected from the group consisting of hydrogen, alkyl, halogen, cyano, nitro, alkoxy, cycloalkyl, and aryl; and
n is 2.

US Pat. No. 10,428,074

PYRROLE HETEROARYL RING DERIVATIVE AND METHOD OF USE THEREOF

Jiangsu Hengrui Medicine ...

4. A process for preparing (3aR,5S,6aS)-N-(3-methoxyl- 1,2,4-thiadiazol-5-yl)-5-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide:or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof according to claim 1, the process comprising reacting a compound of formula (I), or a pharmaceutically acceptable salt thereof, with compound 34c to obtain (3aR,5S,6aS)-N-(3-methoxyl-1,2,4-thiadiazol-5-yl)-5-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide:or the tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or the pharmaceutically acceptable salt thereof,wherein:
R2 is methyl;
A is nitrogen;
L is a bond;
each of R, R1, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14 is hydrogen; and
each of p, q, s, and t is 1.

US Pat. No. 10,398,689

BENZOPIPERIDINE DERIVATIVE, PREPARATION METHOD THEREOF AND MEDICAL USE THEREOF

Jiangsu Hengrui Medicine ...

1. A compound of formula (I):
or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof,
wherein:
ring A is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl;
ring B is aryl or heteroaryl;
each R1 is identical or different and each is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxy, amino, cycloalkyl, halogen, cyano, carboxy, aldehyde, hydroxy, and nitro, wherein the alkyl cycloalkyl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, amino, nitro, cyano, hydroxy, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl;
each R2 is identical or different and each is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxy, amino, cycloalkyl, halogen, cyano, carboxy, aldehyde, hydroxy, nitro, aryl and heteroaryl, wherein the alkyl, cycloalkyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, amino, nitro, cyano, hydroxy, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl;
each R3 is identical or different and each is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxy, amino, cycloalkyl, halogen, cyano, carboxy, aldehyde, hydroxy, and nitro wherein the alkyl and cycloalkyl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, amino, nitro, cyano, hydroxy, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl;
each R4 is identical or different and each is independently selected from the group consisting of hydrogen, alkyl, deuteroalkyl, haloalkyl, hydroxyalkyl, alkoxy, amino, cycloalkyl, halogen, cyano, carboxy, aldehyde, hydroxy, and nitro wherein the alkyl and cycloalkyl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, amino, nitro, cyano, hydroxy, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxy, amino, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R6 is selected from the group consisting of hydrogen, alkyl, hydroxy, halogen, cyano, amino, nitro, and alkoxy;
m is 0, 1, 2 or 3;
n is 0, 1, 2, 3 or 4;
x is 0, 1, 2 or 3; and
y is 0, 1, 2, 3, 4 or 5.

US Pat. No. 10,385,060

PIPERIDINE DERIVATIVE AND PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF

Jiangsu Hengrui Medicine ...

1. A method for treating an estrogen receptor mediated or dependent disease or condition in a subject in need thereof, wherein the estrogen receptor mediated or dependent disease or disorder is cancer selected from the group consisting of breast cancer, endometrial cancer, cervical cancer, prostate cancer, ovarian cancer, uterine cancer, the method comprising administering to the subject a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers, diluents, or excipients, and a compound of formula (I):
or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof,
wherein:
ring A is selected from the group consisting of:

R is selected from the group consisting of hydrogen, alkyl and cycloalkyl, wherein the alkyl and cycloalkyl are each optionally substituted by one or more groups selected from the group consisting of halogen, amino, cyano, hydroxy, alkoxy, carboxy, cycloalkyl, aryl and heteroaryl;
each R1 is identical or different and each is independently selected from the group consisting of hydrogen, alkyl, halogen, cyano and alkoxy, wherein the alkyl and alkoxy are each optionally substituted by one or more groups selected from the group consisting of halogen, amino, cyano and hydroxy;
R2 is selected from the group consisting of alkyl, haloalkyl and cycloalkyl, wherein the alkyl and cycloalkyl are each optionally substituted by one or more groups selected from the group consisting of halogen, amino, cyano, hydroxy, alkoxy, carboxy, cycloalkyl, aryl and heteroaryl;
R3 is selected from the group consisting of hydrogen, alkyl and cycloalkyl, wherein the alkyl and cycloalkyl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, amino, cyano, hydroxy, alkoxy, carboxy and cycloalkyl;
each R4 is identical or different and each is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkoxy, amino, halogen, cyano, carboxy, alkenyl, alkynyl, heterocyclyl, aryl, heteroaryl, —OR5, —NHC(O)OR5 and —NHC(O)NR6R7, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of Rc, alkyl, haloalkyl, hydroxyalkyl, halogen, amino, nitro, cyano, hydroxy, oxo, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl;
Rc is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxy, amino, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxy, amino, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl and —C(O)NR6R7;
R6 and R7 are identical or different and each is independently selected from the group consisting of hydrogen, alkyl, hydroxy, halogen, cyano, amino, nitro, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxy, amino, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
Ra and Rb are identical or different and each is independently selected from the group consisting of hydrogen, alkyl, hydroxy, halogen, cyano, amino, nitro, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxy, amino, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, —OR5, aryl and heteroaryl;
m is 0, 1, 2, 3 or 4; and
n is 0, 1, 2, 3 or 4.

US Pat. No. 10,358,424

SODIUM SALT OF URIC ACID TRANSPORTER INHIBITOR AND CRYSTALLINE FORM THEREOF

Jiangsu Hengrui Medicine ...

1. An isolated sodium 1-((6-bromoquinolin-4-yl)thio)cyclobutane-1-carboxylate of formula (I):

US Pat. No. 10,196,361

SODIUM SALT OF URIC ACID TRANSPORTER INHIBITOR AND CRYSTALLINE FORM THEREOF

Jiangsu Hengrui Medicine ...

1. A crystal form I of a sodium 1-((6-bromoquinolin-4-yl)thio)cyclobutane-1-carboxylate of formula (I):
wherein the crystal form I has a characteristic X-ray powder diffraction spectrum comprising peaks at diffraction angles (2?) of about 19.48, 20.80, 23.16, and 27.54.

US Pat. No. 10,150,739

CRYSTALLINE FORM OF ANDROGEN RECEPTOR INHIBITOR AND PREPARATION METHOD THEREOF

Jiangsu Hengrui Medicine ...

4. A pharmaceutical composition, comprising the crystal form I of the compound of formula (I) according to claim 1, and a pharmaceutically acceptable carrier.
US Pat. No. 10,449,250

ANTI-SCLEROSTIN ANTIBODY, ANTIGEN BINDING FRAGMENT AND MEDICAL USE THEREOF

Jiangsu Hengrui Medicine ...

1. An antibody or antigen-binding fragment thereof that specifically binds to human sclerostin, comprising:(I) a heavy chain variable region comprising a heavy chain complementarity determining region 1 (CDR1), a heavy chain CDR2, and a heavy chain CDR3 having the amino acid sequences of SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, respectively; and
a light chain variable region comprising a light chain CDR1, a light chain CDR2, and a light chain CDR3 having the amino acid sequences of SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, respectively; or
(II) a heavy chain variable region comprising a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3 having the amino acid sequences of SEQ ID NO: 7, SEQ ID NO: 13, and SEQ ID NO: 9, respectively; and
a light chain variable region comprising a light chain CDR1, a light chain CDR2, and a light chain CDR3 having the amino acid sequences of SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, respectively.

US Pat. No. 10,323,037

AMINOPYRIDAZINONE COMPOUNDS AS PROTEIN KINASE INHIBITORS

JIANGSU HENGRUI MEDICINE ...

1. A compound of formula (I), including tautomers, rotamers, geometric isomers, diastereomers, racemates, and enantiomers, a pharmaceutically acceptable salt, a solvate, or a hydrate thereof,
wherein A is selected from the group consisting of CR0 and N; and wherein R0 is selected from the group consisting of hydrogen, halogen, and alkyl;
Ra, Rb, Rc and Rd are independently selected from the group consisting of hydrogen, halogen, and alkoxyl;
B is selected from the group consisting of hydrogen, C1-C6 alkyl, aryl, and B is either unsubstituted or substituted with at least one member selected from the group consisting of halogen, and alkoxyl;
L is alkylene, or absent; and
Y is selected from the group consisting of:
i)

 wherein W is independently selected from the group consisting of halogen, hydroxyl, cyano, alkyl, and alkoxyl;
p=1, 2, or 3;
q=0, 1, or2;
s=0, 1, 2, or 3; and
Z is selected from the group consisting of —NHC(O)R12 and —NHS(O)2R14; and wherein R12 and R14 are independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, and alkynyl;
ii)

 wherein W is independently selected from the group consisting of halogen, hydroxyl, cyano, alkyl, and alkoxyl;
p=1, 2, or 3;
q=0, 1, or 2;
s =0, 1, 2, or 3; and
Z is selected from the group consisting of CN, —C(O)R11, and —S(O)2R13; and wherein R11, and R13 are independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, and alkynyl; or
Z is selected from the group consisting of —C(O)CH?CH2, —C(O)CH?CHCH2N(CH3)2, —C(O)CH?CHCH2N(CH3)(COOC(CH3)3; —C(O)CH?CHCH2NH(CH3), —C(O)CH2CH3, —C(O)CH2CH2CH3,

 C(O)CH2CH2Cl,

 —C(O)CH2CN,

iii)

 wherein W is selected from the group consisting of halogen, hydroxyl, cyano, alkyl, and alkoxyl; and
Z is —NHC(O)R12; and wherein R12 is selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, and alkynyl;
iv)

 wherein W is independently selected from halogen, hydroxyl, cyano, alkyl, and alkoxyl;
p =1 or 2;
s =0, 1, 2, or 3;
Z1 is selected from the group consisting of hydrogen, halogen, cyano, and alkyl; and
Z2 and Z3 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycloalkyl, —CH2O-alkyl, —CH2NR16R17;
wherein R16 and R17 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, and heterocycloalkyl;
wherein heterocycloalkyl is selected from the group consisting of morpholinyl, oxazolidinyl, piperazinyl, piperidinyl, pyrrolidinyl, tetrahydrofuryl, thiomorpholinyl, and indolinyl;
wherein R16 and R17 can combine with N to which they are attached to form a heterocyclic ring selected from the group consisting of morpholinyl, oxazolidinyl, piperazinyl, piperidinyl, pyrrolidinyl, thiomorpholinyl and indolinyl; and
wherein Z1 and Z2 can join together to form a bond; and
v) bicyclo[3.2.1]octanyl.
US Pat. No. 10,258,584

PREGABALIN SUSTAINED-RELEASE PREPARATION

Jiangsu Hengrui Medicine ...

1. An oral sustained-release preparation comprising pregabalin, a salt or hydrate thereof as an active ingredient, a gel matrix material and a swelling material, wherein the gel matrix material comprises alginate, and the swelling material comprises polyoxyethylene, wherein a release amount of the active ingredient is less than 15% within 1 hour and more than 80% at 16 hours as determined by an in vitro dissolution test of the oral sustained-release preparation.