Compounds and compositions for treating conditions associated with nlrp activity

A method of treating a disease, disorder or condition that is any one of:

• a metabolic disorder;
• a disease of the central nervous system;
• lung disease;
• asthma, COPD or pulmonary idiopathic fibrosis;
• liver disease;
• pancreatic disease;
• kidney disease;
• intestinal disease;
• skin disease;
• musculoskeletal disease;
• vessel disorder;
• disorder of the bones;
• eye disease;
• caused by viral infection;
• autoimmune disease;
• cancer or aging;
• the method comprising administering to a subject in need of such treatment an effective amount of 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:
• thiophenyl optionally substituted with 1 or 2 R1 and optionally substituted with 1 or 2 R2;
• phenyl optionally substituted with 1 or 2 R1 and optionally substituted with 1 or 2 R2;
• thiazolyl optionally substituted with 1 or 2 R1 and optionally substituted with 1 or 2 R2;
• oxazolyl optionally substituted with 1 or 2 R1 and optionally substituted with 1 or 2 R2;
• pyridyl optionally substituted with 1 or 2 R1 and optionally substituted with 1 or 2 R2;
• pyrazolyl optionally substituted with 1 or 2 R1 and optionally substituted with 1 or 2 R2;
• B is phenyl, pyridyl, or pyrimidinyl;
• wherein
• at least one R6 is ortho to the bond connecting the B ring to the C(R4R5) group of Formula AA;
• R1 and R2 are each independently selected from C1-C6 alkyl, halo, CN, COC1-C6 alkyl, CO2C1-C6 alkyl, C6-C10 aryl, S(O)C1-C6 alkyl, 5- to 10-membered heteroaryl, and 3- to 7-membered heterocycloalkyl,
• wherein the C1-C6 alkyl and 3- to 7-membered heterocycloalkyl is optionally substituted with one or more substituents each independently selected from hydroxy and oxo;
• R6 and R1 are each independently selected from C1-C6 alkyl, C1-C6 alkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, CONR8R9, and 3- to 7-membered heterocycloalkyl,
• wherein the C1-C6 alkyl and 3- to 7-membered heterocycloalkyl is optionally substituted with one or more substituents each independently selected from hydroxy or oxo,
• or at least one pair of R6 and Ron adjacent atoms, taken together with the atoms connecting them, independently form at least one C5-C8 carbocyclic ring, wherein the carbocyclic ring is optionally independently substituted with one or more hydroxy or oxo;
• each of R4 and R5 is independently selected from hydrogen and C1-C6 alkyl;
• R10 is C1-C6 alkyl;
• each of R1 and R9 at each occurrence is independently selected from hydrogen, C1-C6 alkyl, (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 or 3- to 7-membered heterocycloalkyl;
• or R1 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;
• R3 is hydrogen,
• or a pharmaceutically acceptable salt thereof.