US 2023/0051589 A1Published application

Compounds and compositions for treating conditions associated with nlrp activity

AssigneeNovartis AG

InventorsLuigi FRANCHI, Shomir GHOSH, Gary GLICK, Jason KATZ, Anthony William OPIPARI, Jr., William ROUSH, Hans Martin SEIDEL, Dong-Ming SHEN, Shankar VENKATRAMAN, David Guenther WINKLER

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Abstract

In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured: Formula AA or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formula A can be as defined anywhere herein.

Claims198

Dependent claims

A compound of Formula AA

wherein
m=0, 1, or 2;
n=0, 1, or 2;
o=1 or 2;
p=0, 1, 2, or 3,
wherein
A is a 5- to 10-membered monocyclic or bicyclic heteroaryl or a C6-C10 monocyclic or bicyclic aryl;
B is a 5-membered heteroaryl, a 7-10 membered monocyclic or bicyclic heteroaryl, or a C6-C10 monocyclic or bicyclic aryl;
wherein at least one R6 is ortho to the bond connecting the B ring to the NH(CO) group of Formula AA;
R1 and R2 are each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NR8R9, C(O)R13, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O)C1-C6 alkyl, S(O2)NR11R12, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl,
wherein the C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl is optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R15, C1-C6 haloalkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C3-C7 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), and OCO(3- to 7-membered heterocycloalkyl);
wherein each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the R1 or R2 C3-C7 cycloalkyl or of the R1 or R2 3- to 7-membered heterocycloalkyl is further optionally independently substituted with one to three hydroxy, —O(C0-C3 alkylene)C6-C10 aryl, halo, NR8R9, or oxo;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
or one pair of R1 and R2 on adjacent atoms, taken together with the atoms connecting them, independently form one monocyclic or bicyclic C4-C12 carbocyclic ring or one monocyclic or bicyclic 5- to-12-membered heterocyclic ring containing 1-3 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents each independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C10 cycloalkyl, NR8R9, ═NR10, CN, COOC1-C6 alkyl, 0S(O2)C6-C10 aryl, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR8R9,
wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, and 3- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C1-C6 alkoxy, oxo, NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
R6 and R7 are each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,
wherein R6 and R7 are each optionally substituted with one or more substituents independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryloxy, and S(O2)C1-C6 alkyl;
and wherein the C1-C6 alkyl or C1-C6 alkoxy that R6 or R7 is substituted with is optionally substituted with one or more hydroxyl, C6-C10 aryl or NR8R9, or wherein R6 or R7 is optionally fused to a five- to -seven-membered carbocyclic ring or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur and nitrogen;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
or at least one pair of R6 and R7 on adjacent atoms, taken together with the atoms connecting them, independently form at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing 1 or 2 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, CH2NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
R10 is C1-C6 alkyl;
each of R8 and R9 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, (C═NR13)NR11R12, S(O2)C1-C6 alkyl, S(O2)NR11R12, COR13, CO2R13 and CONR11R12;
wherein the C1-C6 alkyl is optionally substituted with one or more hydroxy, halo, C1-C6 alkoxy, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR11R12;
or R8 and R9 taken together with the nitrogen they are attached to form a 3- to 10-membered monocyclic or bicyclic ring optionally containing one or more heteroatoms in addition to the nitrogen they are attached to, wherein the ring is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
R13 is C1-C6 alkyl, C1-C6 haloalkyl, or —(Z1—Z2)a1—Z3;
each of R11 and R12 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, and —(Z1—Z2)a1—Z3;
a1 is 0-10 (e.g., 0-4);
each Z1 is independently C1-C6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy;
each Z2 is independently a bond, NH, N(C1-C6 alkyl), —O—, —S—, or 5-10 membered heteroarylene;
Z3 is independently C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
R3 is selected from hydrogen and C1-C6 alkyl;
R14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl or C6-C10 monocyclic or bicyclic aryl, wherein each C1-C6 alkyl, aryl or heteroaryl is optionally independently substituted with 1 or 2 R6,
R15 is —(Z4—Z5)a2—Z6;
a2 is an integer selected from 1-10 (e.g., 1-5);
each Z4 is independently selected from —O—, —S—, —NH—, and —N(C1-C3 alkyl)-;
provided that the Z4 group directly attached to R1 or R2 is —O— or —S—;
each Z5 is independently C1-C6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy;
and
Z6 is OH, OC1-C6 alkyl, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NHC(O)(C1-C6 alkyl), NHC(O)(C1-C6 alkoxy), or an optionally substituted group selected from the group consisting of:
C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
or a pharmaceutically acceptable salt thereof;
provided that the compound is other than:

39 more elements

A compound of Formula AA

wherein
m=0, 1, or 2;
n=0, 1, or 2;
o=1 or 2;
p=0, 1, 2, or 3,
wherein
A is a 5- to 10-membered monocyclic or bicyclic heteroaryl or a C6-C10 monocyclic or bicyclic aryl;
B is a 5-membered heteroaryl, a 7-10 membered monocyclic or bicyclic heteroaryl, or a C6-C10 monocyclic or bicyclic aryl;
wherein at least one R6 is ortho to the bond connecting the B ring to the NH(CO) group of Formula AA;
R1 and R2 are each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO—C6-C10 aryl, CO(5- to 10-membered heteroaryl);
CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, NHCOC1-C6 alkyl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), NHCOC2-C6 alkynyl, NHCOOCC1-C6 alkyl, NH—(C═NR13)NR11R12, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O)C1-C6 alkyl, S(O2)NR11R12, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl,
wherein the C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl is optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R15, C1-C6 haloalkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C3-C7 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), NHCOC1-C6 alkyl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC2-C6 alkynyl;
wherein each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the R1 or R2 C3-C7 cycloalkyl or of the R1 or R2 3- to 7-membered heterocycloalkyl is further optionally independently substituted with one to three hydroxy, —O(C0-C3 alkylene)C6-C10 aryl, halo, NR8R9, or oxo;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl) and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
or one pair of R1 and R2 on adjacent atoms, taken together with the atoms connecting them, independently form one monocyclic or bicyclic C4-C12 carbocyclic ring or one monocyclic or bicyclic 5- to-12-membered heterocyclic ring containing 1-3 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents each independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C10 cycloalkyl, NR8R9, ═NR10, CN, COOC1-C6 alkyl, OS(O2)C6-C10 aryl, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR8R9,
wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, and 3- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C1-C6 alkoxy, oxo, NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
R6 and R7 are each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,
wherein R6 and R7 are each optionally substituted with one or more substituents independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), NHCOC1-C6 alkyl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), NHCOC2-C6 alkynyl, C6-C10 aryloxy, and S(O2)C1-C6 alkyl;
and wherein the C1-C6 alkyl or C1-C6 alkoxy that R6 or R7 is substituted with is optionally substituted with one or more hydroxyl, C6-C10 aryl or NR8R9, or wherein R6 or R7 is optionally fused to a five- to -seven-membered carbocyclic ring or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur and nitrogen;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
or at least one pair of R6 and R7 on adjacent atoms, taken together with the atoms connecting them, independently form at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing 1 or 2 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, CH2NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
R10 is C1-C6 alkyl;
each of R8 and R9 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, (C═NR13)NR11R12, S(O2)C1-C6 alkyl, S(O2)NR11R12, COR13, CO2R13 and CONR11R12;
wherein the C1-C6 alkyl is optionally substituted with one or more hydroxy, halo, C1-C6 alkoxy, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR11R12;
or R8 and R9 taken together with the nitrogen they are attached to form a 3- to 7-membered ring optionally containing one or more heteroatoms in addition to the nitrogen they are attached to;
R13 is C1-C6 alkyl, C1-C6 haloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl;
each of R11 and R12 at each occurrence is independently selected from hydrogen and C1-C6 alkyl;
R3 is selected from hydrogen and C1-C6 alkyl;
R14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl or C6-C10 monocyclic or bicyclic aryl, wherein each C1-C6 alkyl, aryl or heteroaryl is optionally independently substituted with 1 or 2 R6,
R15 is —(Z4—Z5)a2—Z6;
a2 is an integer selected from 1-10 (e.g., 1-5);
each Z4 is independently selected from —O—, —S—, —NH—, and —N(C1-C3 alkyl)-;
provided that the Z4 group directly attached to R1 or R2 is —O— or —S—;
each Z5 is independently C1-C6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy;
and
Z6 is OH, OC1-C6 alkyl, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NHC(O)(C1-C6 alkyl), NHC(O)(C1-C6 alkoxy), or an optionally substituted group selected from the group consisting of:
C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
or a pharmaceutically acceptable salt thereof;
provided that the compound is other than:

36 more elements

A compound of Formula AA

wherein the
moiety is as defined for (AA-1), (AA-2), (AA-3), or (AA-4) below:
(AA-1):
A is a 5- to 10-membered monocyclic or bicyclic heteroaryl or a C7-C10 bicyclic aryl;
m=0, 1, or 2;
and
n=0, 1, or 2;
(AA-2):
A is phenyl;
m=0, 1, or 2;
and
n=0, 1, or 2, provided that m+n=0, 2, 3, or 4;
(AA-3):
(AA-4):
B is a 5-membered heteroaryl, a 7-10 membered monocyclic or bicyclic heteroaryl, or a C6-C10 monocyclic or bicyclic aryl;
wherein at least one R6 is ortho to the bond connecting the B ring to the NH(CO) group of Formula AA;
o=1 or 2;
p=0, 1, 2, or 3;
when (AA-1), (AA-2), or (AA-3) apply,
R1 and R2 are each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO—C6-C10 aryl, CO(5- to 10-membered heteroaryl);
CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, NHCOC1-C6 alkyl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), NHCOC2-C6 alkynyl, NHCOOCC1-C6 alkyl, NH—(C═NR13)NR11R12, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O)C1-C6 alkyl, S(O2)NR11R12, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl,
wherein the C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl is optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R15, C1-C6 haloalkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C3-C7 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), NHCOC1-C6 alkyl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC2-C6 alkynyl;
wherein each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the R1 or R2 C3-C7 cycloalkyl or of the R1 or R2 3- to 7-membered heterocycloalkyl is further optionally independently substituted with one to three hydroxy, —O(C0-C3 alkylene)C6-C10 aryl, halo, NR8R9, or oxo;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl) and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
or one pair of R1 and R2 on adjacent atoms, taken together with the atoms connecting them, independently form one monocyclic or bicyclic C4-C12 carbocyclic ring or one monocyclic or bicyclic 5- to-12-membered heterocyclic ring containing 1-3 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents each independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C10 cycloalkyl, NR8R9, ═NR10, CN, COOC1-C6 alkyl, OS(O2)C6-C10 aryl, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR8R9,
wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, and 3- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C1-C6 alkoxy, oxo, NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
OR
when (AA-4) applies, R1′ is selected from the group consisting of:
methyl;
C2-C6 alkyl;
C1-C6 haloalkyl;
C1-C6 alkoxy;
C1-C6 haloalkoxy;
halo;
CN;
NO2;
COC1-C6 alkyl;
CO—C6-C10 aryl;
CO(5- to 10-membered heteroaryl);
CO2C1-C6 alkyl;
CO2C3-C8 cycloalkyl;
OCOC1-C6 alkyl;
OCOC6-C10 aryl;
OCO(5- to 10-membered heteroaryl);
OCO(3- to 7-membered heterocycloalkyl);
C6-C10 aryl;
5- to 10-membered heteroaryl;
NH2;
NHC1-C6 alkyl;
N(C1-C6 alkyl)2;
NHCOC1-C6 alkyl;
NHCOC6-C10 aryl;
NHCO(5- to 10-membered heteroaryl);
NHCO(3- to 7-membered heterocycloalkyl);
NHCOC2-C6 alkynyl;
NHCOOC1-C6 alkyl;
NH—(C═NR13)NR11R12;
CONR8R9;
SF5;
SC1-C6 alkyl;
S(O2)C1-C6 alkyl;
S(O)C1-C6 alkyl;
S(O2)NR11R12;
C3-C7 cycloalkyl;
and 3- to 7-membered heterocycloalkyl,
wherein when R1′ is methyl, R1′ is substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R15, C1-C6 haloalkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C3-C7 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), and OCO(3- to 7-membered heterocycloalkyl);
wherein when R1′ is selected from the group consisting of C2-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl, R1′ is optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R15, C1-C6 haloalkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C3-C7 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), NHCOC1-C6 alkyl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC2-C6 alkynyl;
wherein each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the R1′ C3-C7 cycloalkyl or of the R1′ 3- to 7-membered heterocycloalkyl is further optionally independently substituted with one to three hydroxy, —O(C0-C3 alkylene)C6-C10 aryl, halo, NR8R9, or oxo;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl) and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
R6 and R7 are each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,
wherein R6 and R7 are each optionally substituted with one or more substituents independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), NHCOC1-C6 alkyl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), NHCOC2-C6 alkynyl, C6-C10 aryloxy, and S(O2)C1-C6 alkyl;
and wherein the C1-C6 alkyl or C1-C6 alkoxy that R6 or R7 is substituted with is optionally substituted with one or more hydroxyl, C6-C10 aryl or NR8R9, or wherein R6 or R7 is optionally fused to a five- to -seven-membered carbocyclic ring or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur and nitrogen;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
or at least one pair of R6 and R7 on adjacent atoms, taken together with the atoms connecting them, independently form at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing 1 or 2 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, CH2NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
R10 is C1-C6 alkyl;
each of R8 and R9 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, (C═NR13)NR11R12, S(O2)C1-C6 alkyl, S(O2)NR11R12, COR13, CO2R13 and CONR11R12;
wherein the C1-C6 alkyl is optionally substituted with one or more hydroxy, halo, C1-C6 alkoxy, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR11R12;
or R8 and R9 taken together with the nitrogen they are attached to form a 3- to 7-membered ring optionally containing one or more heteroatoms in addition to the nitrogen they are attached to;
R13 is C1-C6 alkyl, C1-C6 haloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl;
each of R11 and R12 at each occurrence is independently selected from hydrogen and C1-C6 alkyl;
R3 is selected from hydrogen and C1-C6 alkyl (e.g., R3 is selected from hydrogen and methyl);
R14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl or C6-C10 monocyclic or bicyclic aryl, wherein each C1-C6 alkyl, aryl or heteroaryl is optionally independently substituted with 1 or 2 R6;
R15 is —(Z4—Z5)2a—Z6;
a2 is an integer selected from 1-10 (e.g., 1-5);
each Z4 is independently selected from —O—, —S—, —NH—, and —N(C1-C3 alkyl)-;
provided that the Z4 group directly attached to R1 or R2 is —O— or —S—;
each Z5 is independently C1-C6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy;
and
Z6 is OH, OC1-C6 alkyl, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NHC(O)(C1-C6 alkyl), NHC(O)(C1-C6 alkoxy), or an optionally substituted group selected from the group consisting of:
C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
or a pharmaceutically acceptable salt thereof.

88 more elements

A compound of Formula AA

wherein
m=1 or 2;
n=1 or 2;
o=1 or 2;
p=0, 1, 2, or 3,
wherein
A is a 5- to 10-membered monocyclic or bicyclic heteroaryl or a C6-C10 monocyclic or bicyclic aryl;
B is a 5-membered heteroaryl, a 7-10 membered monocyclic or bicyclic heteroaryl, or a C6-C10 monocyclic or bicyclic aryl;
wherein at least one R6 is ortho to the bond connecting the B ring to the NH(CO) group of Formula AA;
one pair of R1 and R2 are on adjacent atoms, and taken together with the atoms connecting them, independently form one monocyclic or bicyclic C4-C12 carbocyclic ring or one monocyclic or bicyclic 5- to-12-membered heterocyclic ring containing 1-3 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents each independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C10 cycloalkyl, NR8R9, ═NR10, CN, COOC1-C6 alkyl, OS(O2)C6-C10 aryl, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR8R9,
wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, and 3- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C1-C6 alkoxy, oxo, NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
each of R1 and R2 that are not taken together with the atoms connecting them to form at least one ring is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NR8R9, C(O)R13, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O)C1-C6 alkyl, S(O2)NR11R12, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl,
wherein the C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl is optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R15, C1-C6 haloalkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C3-C7 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), and OCO(3- to 7-membered heterocycloalkyl);
wherein each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the R1 or R2 C3-C7 cycloalkyl or of the R1 or R2 3- to 7-membered heterocycloalkyl is further optionally independently substituted with one to three hydroxy, —O(C0-C3 alkylene)C6-C10 aryl, halo, NR8R9, or oxo;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
R6 and R7 are each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,
wherein R6 and R7 are each optionally substituted with one or more substituents independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryloxy, and S(O2)C1-C6 alkyl;
and wherein the C1-C6 alkyl or C1-C6 alkoxy that R6 or R7 is substituted with is optionally substituted with one or more hydroxyl, C6-C10 aryl or NR8R9, or wherein R6 or R7 is optionally fused to a five- to -seven-membered carbocyclic ring or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur and nitrogen;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
or at least one pair of R6 and R7 on adjacent atoms, taken together with the atoms connecting them, independently form at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing 1 or 2 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, CH2NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
R10 is C1-C6 alkyl;
each of R8 and R9 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, (C═NR13)NR11R12, S(O2)C1-C6 alkyl, S(O2)NR11R12, COR13, CO2R13 and CONR11R12;
wherein the C1-C6 alkyl is optionally substituted with one or more hydroxy, halo, C1-C6 alkoxy, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR11R12;
or R8 and R9 taken together with the nitrogen they are attached to form a 3- to 10-membered monocyclic or bicyclic ring optionally containing one or more heteroatoms in addition to the nitrogen they are attached to, wherein the ring is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
R13 is C1-C6 alkyl, C1-C6 haloalkyl, or —(Z1—Z2)a1—Z3;
each of R11 and R12 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, and —(Z1—Z2)a1—Z3;
a1 is 0-10 (e.g., 0-4);
each Z1 is independently C1-C6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy;
each Z2 is independently a bond, NH, N(C1-C6 alkyl), —O—, —S—, or 5-10 membered heteroarylene;
Z3 is independently C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
R3 is selected from hydrogen and C1-C6 alkyl (e.g., R3 is selected from hydrogen and methyl);
R14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl or C6-C10 monocyclic or bicyclic aryl, wherein each C1-C6 alkyl, aryl or heteroaryl is optionally independently substituted with 1 or 2 R6,
R15 is —(Z4—Z5)a2—Z6;
a2 is an integer selected from 1-10 (e.g., 1-5);
each Z4 is independently selected from —O—, —S—, —NH—, and —N(C1-C3 alkyl)-;
provided that the Z4 group directly attached to R1 or R2 is —O— or —S—;
each Z5 is independently C1-C6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy;
and
Z6 is OH, OC1-C6 alkyl, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NHC(O)(C1-C6 alkyl), NHC(O)(C1-C6 alkoxy), or an optionally substituted group selected from the group consisting of:
C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
or a pharmaceutically acceptable salt thereof.

38 more elements

A compound of Formula AA

wherein
m=1 or 2;
n=1 or 2;
o=1 or 2;
p=0, 1, 2, or 3,
wherein
A is a 5- to 10-membered monocyclic or bicyclic heteroaryl or a C6-C10 monocyclic or bicyclic aryl;
B is a 5-membered heteroaryl, a 7-10 membered monocyclic or bicyclic heteroaryl, or a C6-C10 monocyclic or bicyclic aryl;
wherein at least one R6 is ortho to the bond connecting the B ring to the NH(CO) group of Formula AA;
one pair of R1 and R2 are on adjacent atoms, taken together with the atoms connecting them, independently form one monocyclic or bicyclic C4-C12 carbocyclic ring or one monocyclic or bicyclic 5- to-12-membered heterocyclic ring containing 1-3 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents each independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C10 cycloalkyl, NR8R9,═NR10,CN, COOC1-C6 alkyl, OS(O2)C6-C10 aryl, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR8R9,
wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, and 3- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C1-C6 alkoxy, oxo, NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
each of R1 and R2 that are not taken together with the atoms connecting them to form at least one ring is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO—C6-C10 aryl, CO(5- to 10-membered heteroaryl);
CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, NHCOC1-C6 alkyl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), NHCOC2-C6 alkynyl, NHCOOCC1-C6 alkyl, NH—(C═NR13)NR11R12, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O)C1-C6 alkyl, S(O2)NR11R12, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl,
wherein the C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl is optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R15, C1-C6 haloalkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C3-C7 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), NHCOC1-C6 alkyl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC2-C6 alkynyl;
wherein each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the R1 or R2 C3-C7 cycloalkyl or of the R1 or R2 3- to 7-membered heterocycloalkyl is further optionally independently substituted with one to three hydroxy, —O(C0-C3 alkylene)C6-C10 aryl, halo, NR8R9, or oxo;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl) and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
R6 and R7 are each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,
wherein R6 and R7 are each optionally substituted with one or more substituents independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), NHCOC1-C6 alkyl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), NHCOC2-C6 alkynyl, C6-C10 aryloxy, and S(O2)C1-C6 alkyl;
and wherein the C1-C6 alkyl or C1-C6 alkoxy that R6 or R7 is substituted with is optionally substituted with one or more hydroxyl, C6-C10 aryl or NR8R9, or wherein R6 or R7 is optionally fused to a five- to -seven-membered carbocyclic ring or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur and nitrogen;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, NHCOC6-C10 aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
or at least one pair of R6 and R7 on adjacent atoms, taken together with the atoms connecting them, independently form at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing 1 or 2 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, CH2NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
R10 is C1-C6 alkyl;
each of R8 and R9 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, (C═NR13)NR11R12, S(O2)C1-C6 alkyl, S(O2)NR11R12, COR13, CO2R13 and CONR11R12;
wherein the C1-C6 alkyl is optionally substituted with one or more hydroxy, halo, C1-C6 alkoxy, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR11R12;
or R8 and R9 taken together with the nitrogen they are attached to form a 3- to 7-membered ring optionally containing one or more heteroatoms in addition to the nitrogen they are attached to;
R13 is C1-C6 alkyl, C1-C6 haloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl;
each of R11 and R12 at each occurrence is independently selected from hydrogen and C1-C6 alkyl;
R3 is selected from hydrogen and C1-C6 alkyl (e.g., R3 is selected from hydrogen and methyl);
R14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl or C6-C10 monocyclic or bicyclic aryl, wherein each C1-C6 alkyl, aryl or heteroaryl is optionally independently substituted with 1 or 2 R6,
R15 is —(Z4—Z5)a2—Z6;
a2 is an integer selected from 1-10 (e.g., 1-5);
each Z4 is independently selected from —O—, —S—, —NH—, and —N(C1-C3 alkyl)-;
provided that the Z4 group directly attached to R1 or R2 is —O— or —S—;
each Z5 is independently C1-C6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy;
and
Z6 is OH, OC1-C6 alkyl, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NHC(O)(C1-C6 alkyl), NHC(O)(C1-C6 alkoxy), or an optionally substituted group selected from the group consisting of:
C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
or a pharmaceutically acceptable salt thereof.

35 more elements

A compound of Formula AA:

wherein the
moiety is as defined for (AA-1), (AA-2), (AA-3), or (AA-4) below:
(AA-1):
A is a 5- to 10-membered monocyclic or bicyclic heteroaryl or a C7-C10 bicyclic aryl;
m=0, 1, or 2;
and
n=0, 1, or 2;
(AA-2):
A is phenyl;
m=0, 1, or 2;
and
n=0, 1, or 2, provided that m+n=0, 2, 3, or 4;
(AA-3):
(AA-4):
B is a 5-membered heteroaryl, a 7-10 membered monocyclic or bicyclic heteroaryl, or a C6-C10 monocyclic or bicyclic aryl;
wherein at least one R6 is ortho to the bond connecting the B ring to the NH(CO) group of Formula AA;
o=1 or 2;
p=0, 1, 2, or 3;
when (AA-1), (AA-2), or (AA-3) applies,
R1 and R2 are each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NR8R9, C(O)R13, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O)C1-C6 alkyl, S(O2)NR11R12, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl,
wherein the C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl is optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R15, C1-C6 haloalkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C3-C7 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), and OCO(3- to 7-membered heterocycloalkyl);
wherein each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the R1 or R2 C3-C7 cycloalkyl or of the R1 or R2 3- to 7-membered heterocycloalkyl is further optionally independently substituted with one to three hydroxy, —O(C0-C3 alkylene)C6-C10 aryl, halo, NR8R9, or oxo;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
or one pair of R1 and R2 on adjacent atoms, taken together with the atoms connecting them, independently form one monocyclic or bicyclic C4-C12 carbocyclic ring or one monocyclic or bicyclic 5- to-12-membered heterocyclic ring containing 1-3 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents each independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C10 cycloalkyl, NR8R9, ═NR10, CN, COOC1-C6 alkyl, OS(O2)C6-C10 aryl, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR8R9,
wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, and 3- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C1-C6 alkoxy, oxo, NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
OR
when (AA-4) applies, R1′ is selected from the group consisting of:
methyl;
C2-C6 alkyl;
C1-C6 haloalkyl;
C1-C6 alkoxy;
C1-C6 haloalkoxy;
halo;
CN;
NO2;
CO2C1-C6 alkyl;
CO2C3-C8 cycloalkyl;
OCOC1-C6 alkyl;
OCOC6-C10 aryl;
OCO(5- to 10-membered heteroaryl);
OCO(3- to 7-membered heterocycloalkyl);
C6-C10 aryl;
5- to 10-membered heteroaryl;
NR8R9;
C(O)R13;
CONR8R9;
SF5;
SC1-C6 alkyl;
S(O2)C1-C6 alkyl, S(O)C1-C6 alkyl;
S(O2)NR11R12;
C3-C7 cycloalkyl;
and 3- to 7-membered heterocycloalkyl,
wherein when R1′ is methyl, R1′ is substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R15, C1-C6 haloalkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C3-C7 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), and OCO(3- to 7-membered heterocycloalkyl);
and
when R1′ is selected from the group consisting of C2-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl, R1′ is optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R15, C1-C6 haloalkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C3-C7 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), and OCO(3- to 7-membered heterocycloalkyl);
wherein each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the R1′ C3-C7 cycloalkyl or of the R1′ 3- to 7-membered heterocycloalkyl is further optionally independently substituted with one to three hydroxy, halo, —O(C0-C3 alkylene)C6-C10 aryl, NR8R9, or oxo;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
R6 and R7 are each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,
wherein R6 and R7 are each optionally substituted with one or more substituents independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryloxy, and S(O2)C1-C6 alkyl;
and wherein the C1-C6 alkyl or C1-C6 alkoxy that R6 or R7 is substituted with is optionally substituted with one or more hydroxyl, C6-C10 aryl or NR8R9, or wherein R6 or R7 is optionally fused to a five- to -seven-membered carbocyclic ring or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur and nitrogen;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
or at least one pair of R6 and R7 on adjacent atoms, taken together with the atoms connecting them, independently form at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing 1 or 2 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, CH2NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
R10 is C1-C6 alkyl;
each of R8 and R9 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, (C═NR13)NR11R12, S(O2)C1-C6 alkyl, S(O2)NR11R12, COR13, CO2R13 and CONR11R12;
wherein the C1-C6 alkyl is optionally substituted with one or more hydroxy, halo, C1-C6 alkoxy, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR11R12;
or R8 and R9 taken together with the nitrogen they are attached to form a 3- to 10-membered monocyclic or bicyclic ring optionally containing one or more heteroatoms in addition to the nitrogen they are attached to, wherein the ring is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
R13 is C1-C6 alkyl, C1-C6 haloalkyl, or —(Z1—Z2)a1—Z3;
each of R11 and R12 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, and —(Z1—Z2)a1—Z3;
a1 is 0-10 (e.g., 0-4);
each Z1 is independently C1-C6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy;
each Z2 is independently a bond, NH, N(C1-C6 alkyl), —O—, —S—, or 5-10 membered heteroarylene;
Z3 is independently C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
R3 is selected from hydrogen and C1-C6 alkyl (e.g., R3 is selected from hydrogen and methyl);
R15 is —(Z4—Z5)a2—Z6;
a2 is an integer selected from 1-10 (e.g., 1-5);
each Z4 is independently selected from —O—, —S—, —NH—, and —N(C1-C3 alkyl)-;
provided that the Z4 group directly attached to R1 or R2 is —O— or —S—;
each Z5 is independently C1-C6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy;
and
Z6 is OH, OC1-C6 alkyl, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NHC(O)(C1-C6 alkyl), NHC(O)(C1-C6 alkoxy), or an optionally substituted group selected from the group consisting of:
C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
or a pharmaceutically acceptable salt thereof.

79 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/293,781Filed 14 Nov 2019
Priority: 16 Nov 2018
Published: 16 Feb 2023
Term ends: Not estimatedThe source records don’t support an estimate.

Classification50 codes

A61K 31/426
Thiazoles: 1,3-Thiazoles
A61K 31/18
Amides, e.g. hydroxamic acids: sulfonamides
A61K 31/36
Having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel: compounds containing methylenedioxyphenyl groups, e.g. sesamin
A61K 31/381
Having sulfur as a ring hetero atom: having five-membered rings

Family

Application62/768,804Us provisional application · filed 16 Nov 2018
Application62/769,151Us provisional application · filed 19 Nov 2018
Application62/769,165Us provisional application · filed 19 Nov 2018
Application62/795,913Us provisional application · filed 23 Jan 2019
Application62/796,356Us provisional application · filed 24 Jan 2019
Application62/796,361Us provisional application · filed 24 Jan 2019
Application62/802,621Us provisional application · filed 7 Feb 2019
Application62/895,954Us provisional application · filed 4 Sep 2019
US 2023/0051589 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of Formula AA

wherein
m=0, 1, or 2;
n=0, 1, or 2;
o=1 or 2;
p=0, 1, 2, or 3,
wherein
A is a 5- to 10-membered monocyclic or bicyclic heteroaryl or a C6-C10 monocyclic or bicyclic aryl;
B is a 5-membered heteroaryl, a 7-10 membered monocyclic or bicyclic heteroaryl, or a C6-C10 monocyclic or bicyclic aryl;
wherein at least one R6 is ortho to the bond connecting the B ring to the NH(CO) group of Formula AA;
R1 and R2 are each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NR8R9, C(O)R13, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O)C1-C6 alkyl, S(O2)NR11R12, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl,
wherein the C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl is optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R15, C1-C6 haloalkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C3-C7 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), and OCO(3- to 7-membered heterocycloalkyl);
wherein each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the R1 or R2 C3-C7 cycloalkyl or of the R1 or R2 3- to 7-membered heterocycloalkyl is further optionally independently substituted with one to three hydroxy, —O(C0-C3 alkylene)C6-C10 aryl, halo, NR8R9, or oxo;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
or one pair of R1 and R2 on adjacent atoms, taken together with the atoms connecting them, independently form one monocyclic or bicyclic C4-C12 carbocyclic ring or one monocyclic or bicyclic 5- to-12-membered heterocyclic ring containing 1-3 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents each independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C10 cycloalkyl, NR8R9, ═NR10, CN, COOC1-C6 alkyl, 0S(O2)C6-C10 aryl, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR8R9,
wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C10 aryl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C10 cycloalkyl, and 3- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C1-C6 alkoxy, oxo, NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
R6 and R7 are each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,
wherein R6 and R7 are each optionally substituted with one or more substituents independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, CONR8R9, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C6-C10 aryloxy, and S(O2)C1-C6 alkyl;
and wherein the C1-C6 alkyl or C1-C6 alkoxy that R6 or R7 is substituted with is optionally substituted with one or more hydroxyl, C6-C10 aryl or NR8R9, or wherein R6 or R7 is optionally fused to a five- to -seven-membered carbocyclic ring or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur and nitrogen;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;
or at least one pair of R6 and R7 on adjacent atoms, taken together with the atoms connecting them, independently form at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing 1 or 2 heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, CH2NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9;
R10 is C1-C6 alkyl;
each of R8 and R9 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, (C═NR13)NR11R12, S(O2)C1-C6 alkyl, S(O2)NR11R12, COR13, CO2R13 and CONR11R12;
wherein the C1-C6 alkyl is optionally substituted with one or more hydroxy, halo, C1-C6 alkoxy, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR11R12;
or R8 and R9 taken together with the nitrogen they are attached to form a 3- to 10-membered monocyclic or bicyclic ring optionally containing one or more heteroatoms in addition to the nitrogen they are attached to, wherein the ring is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
R13 is C1-C6 alkyl, C1-C6 haloalkyl, or —(Z1—Z2)a1—Z3;
each of R11 and R12 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, and —(Z1—Z2)a1—Z3;
a1 is 0-10 (e.g., 0-4);
each Z1 is independently C1-C6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy;
each Z2 is independently a bond, NH, N(C1-C6 alkyl), —O—, —S—, or 5-10 membered heteroarylene;
Z3 is independently C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
R3 is selected from hydrogen and C1-C6 alkyl;
R14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl or C6-C10 monocyclic or bicyclic aryl, wherein each C1-C6 alkyl, aryl or heteroaryl is optionally independently substituted with 1 or 2 R6,
R15 is —(Z4—Z5)a2—Z6;
a2 is an integer selected from 1-10 (e.g., 1-5);
each Z4 is independently selected from —O—, —S—, —NH—, and —N(C1-C3 alkyl)-;
provided that the Z4 group directly attached to R1 or R2 is —O— or —S—;
each Z5 is independently C1-C6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy;
and
Z6 is OH, OC1-C6 alkyl, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NHC(O)(C1-C6 alkyl), NHC(O)(C1-C6 alkoxy), or an optionally substituted group selected from the group consisting of:
C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;
or a pharmaceutically acceptable salt thereof;
provided that the compound is other than:

39 more elements

Facts

Application

17/293,781Filed 14 Nov 2019

Priority

16 Nov 2018

Published

16 Feb 2023

Term ends

Not estimatedThe source records don’t support an estimate.

Classification50 codes

A61K 31/426
Thiazoles: 1,3-Thiazoles
A61K 31/18
Amides, e.g. hydroxamic acids: sulfonamides
A61K 31/36
Having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel: compounds containing methylenedioxyphenyl groups, e.g. sesamin
A61K 31/381
Having sulfur as a ring hetero atom: having five-membered rings

Family

Application62/768,804Us provisional application · filed 16 Nov 2018

Application62/769,151Us provisional application · filed 19 Nov 2018

Application62/769,165Us provisional application · filed 19 Nov 2018

Application62/795,913Us provisional application · filed 23 Jan 2019

Application62/796,356Us provisional application · filed 24 Jan 2019

Application62/796,361Us provisional application · filed 24 Jan 2019

Application62/802,621Us provisional application · filed 7 Feb 2019

Application62/895,954Us provisional application · filed 4 Sep 2019

US 2023/0051589 A1This patent

From the US filing history. Foreign family members aren’t listed.