US 11,724,992 B2
Compounds and compositions for treating conditions associated with NLRP activity
Luigi Franchi, Ann Arbor, MI (US); Shomir Ghosh, Brookline, MA (US); Gary Glick, Ann Arbor, MI (US); Jason Katz, Newton, MA (US); Anthony William Opipari, Jr., Dexter, MI (US); William Roush, Boston, MA (US); Hans Martin Seidel, Concord, MA (US); Dong-Ming Shen, Edison, NJ (US); Shankar Venkatraman, Landsdale, PA (US); and David Guenther Winkler, Arlington, MA (US)
Assigned to Novartis AG, Basel (CH)
Filed by Novartis AG, Basel (CH)
Filed on Oct. 7, 2021, as Appl. No. 17/496,375.
Application 17/496,375 is a continuation of application No. 16/632,849, granted, now 11,203,579, previously published as PCT/US2018/043338, filed on Jul. 23, 2018.
Claims priority of provisional application 62/573,894, filed on Oct. 18, 2017.
Claims priority of provisional application 62/536,271, filed on Jul. 24, 2017.
Prior Publication US 2023/0062815 A1, Mar. 2, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 277/36 (2006.01); C07D 215/36 (2006.01); C07D 231/18 (2006.01); C07D 239/26 (2006.01); C07D 263/46 (2006.01); C07D 307/64 (2006.01); C07D 333/34 (2006.01); C07C 307/06 (2006.01); C07D 307/79 (2006.01); C07D 317/62 (2006.01); C07D 487/04 (2006.01); C07C 335/42 (2006.01); C07D 213/71 (2006.01); C07D 231/12 (2006.01); C07D 405/12 (2006.01); C07D 409/12 (2006.01); C07D 417/12 (2006.01); C07D 471/04 (2006.01)
CPC C07D 277/36 (2013.01) [C07C 307/06 (2013.01); C07D 215/36 (2013.01); C07D 231/18 (2013.01); C07D 239/26 (2013.01); C07D 263/46 (2013.01); C07D 307/64 (2013.01); C07D 307/79 (2013.01); C07D 317/62 (2013.01); C07D 333/34 (2013.01); C07D 487/04 (2013.01); C07C 335/42 (2013.01); C07D 213/71 (2013.01); C07D 231/12 (2013.01); C07D 405/12 (2013.01); C07D 409/12 (2013.01); C07D 417/12 (2013.01); C07D 471/04 (2013.01)] 20 Claims
 
1. A compound of Formula AA

OG Complex Work Unit Chemistry
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 5-10-membered heteroaryl or a C6-C10 aryl;
B is a 5-10-membered heteroaryl or a C6-C10 aryl;
wherein
at least one R6 is ortho to the bond connecting the B ring to the NR3(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, NHCOOC1-C6 alkyl, NH—(C═NR3)NR11R12, CONR8R9, SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR11R12, S(O)C1-C6 alkyl, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl,
wherein the C1-C6 alkyl, C1-C6 haloalkyl, 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, COOC1-C6 alkyl, NR8R9, 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), and 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, halo, or oxo;
wherein the 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl, of the R1 or R2 C1-C6 alkyl, the R1 or R2 C1-C6 haloalkyl, the R1 or R2 C3-C7 cycloalkyl, or the R1 or R2 3- to 7-membered heterocycloalkyl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, oxo, and OC1-C6 alkyl;
or at least one pair of R1 and R2 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, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, ═NR10, COOC1-C6 alkyl, C6-C10 aryl, and CONR8R9, wherein the C1-C6 alkyl and C1-C6 alkoxy are optionally substituted with hydroxy, halo, oxo, 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-C7 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, halo, 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 4-to 8-membered heterocyclic ring containing 1 or 2 heteroatoms independently selected from O, N, NR20, 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;
each of R4 and R5 is independently selected from hydrogen and C1-C6 alkyl;
R10 is C1-C6 alkyl;
each of R8 and R9 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, C2-C6alkenyl, C2-C6 alkynyl, (C═NR13)NR11R12, S(O2)C1-C6 alkyl, S(O2)NR11R12, COR13, CO2R13 and CONR11R12; wherein the C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more hydroxy, halo, oxo, C1-C6 alkoxy, C2-C6 alkynyl, C02R13, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, or 3- to 7-membered heterocycloalkyl; 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, 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;
each R3 is independently selected from hydrogen, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkyl, CO2C1-C6 alkyl, and

OG Complex Work Unit Chemistry
wherein the C1-C2 alkylene group is optionally substituted with oxo; and
R14 is hydrogen, C1-C6 alkyl, 5-10-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, 2, or 3 R6;
or a pharmaceutically acceptable salt thereof.