COMPOUNDS FOR INHIBITING NLRP3 AND USES THEREOF

1 .- 30 . (canceled)

31 . A compound of formula (II-h):

or a pharmaceutically acceptable salt, solvate, clathrate, hydrate, stereoisomer, or tautomer thereof, wherein:

each R 2a is independently hydrogen, deuterium, or halogen;

R 1 is C 1 -C 6 alkyl, —(CH 2 ) n —(C 3 -C 10 cycloalkyl), —(CH 2 ) n —(C 6 -C 10 aryl), —(CH 2 ) n -(3- to 8-membered heterocycloalkyl), or —(CH 2 ) n -(5- to 9-membered heteroaryl), wherein the alkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with one or more halo, CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 6 -C 10 aryl , —R 4 OR 5 or —NR 5 R 6 ; and

Y is C 6 -C 10 aryl, wherein the aryl is optionally substituted with one or more halo, —CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, cycloalkyl, or —R 4 OR 5 ;

R 4 is a bond, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl;

each R 5 and R 6 are independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C 6 -C 10 aryl, or 5- to 9-membered heteroaryl, wherein the alkyl is optionally substituted with one or more D; and

n is an integer from 0 to 4.

32 . The compound of claim 31 , wherein R 1 is C 1 -C 6 alkyl optionally substituted with one or more halo, CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 6 -C 10 aryl, —NR 4 R 5 , or —R 4 OR 5 .

33 . The compound of claim 32 , wherein R 1 is C 1 -C 6 alkyl optionally substituted with one or more CN, C 1 -C 6 alkyl, or —R 4 OR 5 .

34 . The compound of claim 31 , wherein each R 2a is independently hydrogen or deuterium.

35 . The compound of claim 31 , wherein at least one R 2a is halogen.

36 . The compound of claim 31 , wherein R 1 is —(CH 2 ) n -(3- to 8-membered heterocycloalkyl), wherein the 3- to 8-membered heterocycloalkyl is substituted with one or more halo.

37 . The compound of claim 31 , wherein n is 0.

38 . The compound of claim 31 , wherein n is 1.

39 . The compound of claim 31 , wherein R 1 is —(CH 2 ) n —(C 3 -C 10 cycloalkyl) substituted with one or more halo, C 1 -C 6 alkyl, or —R 4 OR 5 .

40 . The compound of claim 31 , wherein Y is C 6 -C 10 aryl substituted with one or more halo, C 1 -C 6 alkyl, or —R 4 OR 5 .

41 . The compound of claim 31 , wherein Y is phenyl substituted with one or more halo.

42 . The compound of claim 31 , selected from

or a pharmaceutically acceptable salt, solvate, clathrate, hydrate, stereoisomer, or tautomer thereof.

43 . A pharmaceutical composition comprising a compound of claim 31 , and a pharmaceutically acceptable carrier.

44 . A pharmaceutical composition comprising a compound of claim 42 , and a pharmaceutically acceptable carrier.

45 . A method of treating or preventing an NLRP3-related disease or disorder, comprising administering to the subject the compound of claim 31 .

46 . The method of claim 45 , wherein the NLRP3-related disease or disorder is inflammation, an auto-immune disease, a cancer, an infection, a disease or disorder of the central nervous system, a metabolic disease, a cardiovascular disease, a respiratory disease, a kidney disease, a liver disease, an ocular disease, a skin disease, a lymphatic disease, a rheumatic disease, a psychological disease, graft versus host disease, allodynia, or an NLRP3-related disease in a subject that has been determined to carry a germline or somatic non-silent mutation in NLRP3.

47 . A method of treating or preventing an NLRP3-related disease or disorder, comprising administering to the subject, the compound of claim 42 .

48 . The method of claim 47 , wherein the NLRP3-related disease or disorder is inflammation, an auto-immune disease, a cancer, an infection, a disease or disorder of the central nervous system, a metabolic disease, a cardiovascular disease, a respiratory disease, a kidney disease, a liver disease, an ocular disease, a skin disease, a lymphatic disease, a rheumatic disease, a psychological disease, graft versus host disease, allodynia, or an NLRP3-related disease in a subject that has been determined to carry a germline or somatic non-silent mutation in NLRP3.