US Patent No. 10,039,778

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


Patent No. 10,039,778
Issue Date August 07, 2018
Title Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol Compounds As Targeting Agents Of Asgpr
Inventorship Spiros Liras, Brookline, MA (US)
Vincent Mascitti, Groton, CT (US)
Benjamin Thuma, Old Lyme, CT (US)
Assignee Pfizer Inc., New York, NY (US)

Claim of US Patent No. 10,039,778

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.