Compounds and compositions for treating pathologies associated with NLRP activity

Abstract

In one aspect, a compound of formula AA, or a pharmaceutically acceptable salt thereof, is featured: or a pharmaceutically acceptable salt thereof, wherein the variables set forth in formula A can be as defined anywhere herein. [Case 1] TIFF2022507065001963.tif42170

Claims

1. Formula AA 【Chemistry 1-1】 wherein m=0, 1, or 2; n=0, 1, or 2; During the ceremony, A is a 5- to 10-membered heteroaryl or C ６ ~C １０ is aryl; R １ and R ２ are each independently C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Haloalkoxy, Halo, CN, NO ２ , CO ２ C １ ~C ６ Alkyl, CO ２ C ３ ~C ８ Cycloalkyl, OCOC １ ~C ６ Alkyl, OCOC ６ ~C １０ Aryl, OCO(5-10 membered heteroaryl), OCO(3-7 membered heterocycloalkyl), C ６ ~C １０ Aryl, 5- to 10-membered heteroaryl, NR ８ R ９ , C(O)R １３ , C.O.R. ８ R ９ , SF ５ , SC １ ~C ６ Alkyl, S(O ２ ) C １ ~C ６ Alkyl, S(O ２ ) NR １１ R １２ , S(O)C １ ~C ６ Alkyl, C ３ ~C ７ selected from cycloalkyl and 3- to 7-membered heterocycloalkyl; Said C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Haloalkyl, C ６ ~C １０ Aryl, 5- to 10-membered heteroaryl, C ３ ~C ７ Cycloalkyl and 3- to 7-membered heterocycloalkyl include hydroxy, halo, CN, oxo, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, R １５ , N.R. ８ R ９ , =NR １０ , COOC １ ~C ６ Alkyl, CONR ８ R ９ , 3- to 7-membered heterocycloalkyl, C ６ ~C １０ Aryl, 5- to 10-membered heteroaryl, OCOC １ ~C ６ Alkyl, OCOC ６ ~C １０ optionally substituted with one or more substituents each independently selected from aryl, OCO (5-10 membered heteroaryl), and OCO (3-7 membered heterocycloalkyl); The R １ Or R ２ C ３ ~C ７ Cycloalkyl or the R １ Or R ２ Each C of the 3- to 7-membered heterocycloalkyl １ ~C ６ Alkyl substituents and each C １ ~C ６ The alkoxy substituents may further optionally independently contain 1 to 3 hydroxy, —O(C ０ ~C ３ Alkylene) C ６ ~C １０ Aryl, Halo, NR ８ R ９ or substituted with oxo; The 3- to 7-membered heterocycloalkyl, C ６ ~C １０ Each of the aryl and 5- to 10-membered heteroaryl is optionally selected from halo, C １ ~C ６ Alkyl, and OC １ ~C ６ substituted with one or more substituents independently selected from alkyl; or a pair of R on adjacent atoms １ and R ２ together with the atoms to which they are attached form at least one monocyclic or bicyclic C ４ ~C １２ independently forming a carbocyclic ring or at least one monocyclic or bicyclic 5- to 12-membered heterocyclic ring: a) When each of the adjacent atoms is a carbon atom, the heterocycle is O, NH, NR １３ , S, S(O), and S(O) ２ and b) When one or both of the adjacent atoms is a nitrogen atom, the heterocycle is O, NH, NR １３ , S, S(O), and S(O) ２ (R １ and / or R ２ in addition to the aforementioned nitrogen atom bonded to The carbocycle or heterocycle may optionally independently be selected from the group consisting of hydroxy, halo, oxo, C １ ~C ６ Alkyl, C ２ ~C ６ Alkenyl, C ２ ~C ６ Alkynyl, C １ ~C ６ Alkoxy, OC ３ ~C １０ Cycloalkyl, NR ８ R ９ , =NR １０ , C.N., CO.O.C. １ ~C ６ Alkyl, OS(O ２ ) C ６ ~C １０ Aryl, S(O ２ ) C ６ ~C １０ Aryl, C ６ ~C １０ Aryl, 5- to 10-membered heteroaryl, C ３ ~C １０ cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR ８ R ９ and Said C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, S(O ２ ) C ６ ~C １０ Aryl, C ６ ~C １０ Aryl, 5- to 10-membered heteroaryl, C ３ ~C １０ Cycloalkyl and 3- to 10-membered heterocycloalkyl are optionally substituted with hydroxy, halo, C １ ~C ６ Alkyl, C ２ ~C ６ Alkenyl, C ２ ~C ６ Alkynyl, C ３ ~C １０ Cycloalkyl, C １ ~C ６ Alkoxy, oxo, NR ８ R ９ , =NR １０ , COOC １ ~C ６ Alkyl, C ６ ~C １０ Aryl, and CONR ８ R ９ substituted with one or more substituents each independently selected from R １０ is C １ ~C ６ is alkyl; R in each existence ８ and R ９ each independently represents hydrogen, C １ ~C ６ Alkyl, C ２ ~C ６ Alkenyl, C ３ ~C ７ Cycloalkyl, C １ ~C ６ haloalkyl, (C=NR １３ ) NR １１ R １２ , S(O ２ ) C １ ~C ６ Alkyl, S(O ２ ) NR １１ R １２ , C.O.R. １３ , CO ２ R １３ and CONR １１ R １２ C １ ~C ６ The alkyl may optionally be one or more of hydroxy, halo, C １ ~C ６ Alkoxy, C ６ ~C １０ Aryl, 5- to 10-membered heteroaryl, C ３ ~C ７ cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR １１ R １２ Is replaced by; or R ８ and R ９ are taken together with the nitrogen to which they are attached to form a 3- to 10-membered monocyclic or bicyclic ring which optionally contains one or more heteroatoms in addition to the nitrogen to which they are attached, said ring optionally containing halo, C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Alkoxy, oxo, N(C １ ~C ６ alkyl) ２ , N.H. ２ , NH(C １ ~C ６ substituted with one or more substituents independently selected from alkyl, hydroxy, and hydroxy; R １３ is C １ ~C ６ Alkyl, C １ ~C ６ haloalkyl, or -(Z １ -Z ２ ) ａ１ -Z ３ and R in each existence １１ and R １２ each independently represents hydrogen, C １ ~C ６ Alkyl, and -(Z １ -Z ２ ) ａ１ -Z ３ Selected from: a1 is an integer selected from 0 to 10; Each Z １ is optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy. １ ~C ６ alkylene; Each Z ２ are independently a bond, NH, N(C １ ~C ６ alkyl), —O—, —S—, or 5- to 10-membered heteroarylene; Z ３ are independently ６ ~C １０ Aryl, C ２ ~C ６ Alkenyl, C ２ ~C ６ Alkynyl, C ３ ~C １０ cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which optionally includes halo, C １ ~C ６ Alkyl, C １～６ Haloalkyl, C １ ~C ６ Alkoxy, oxo, N(C １ ~C ６ alkyl) ２ , N.H. ２ , NH(C １ ~C ６ substituted with one or more substituents independently selected from alkyl, hydroxy, and hydroxy; R ３ is hydrogen or methyl; R １５ is -(Z ４ -Z ５ ) ａ２ -Z ６ and a2 is an integer selected from 1 to 10; Each Z ４ are independently —O—, —S—, —NH—, and —N(C １ ~C ３ alkyl)-; However, R １ or R ２ The Z bonded directly to ４ provided that the group is —O— or —S—; Each Z ５ is optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy. １ ~C ６ alkylene; and Z ６ OH, OC １ ~C ６ Alkyl, NH ２ , NH(C １ ~C ６ alkyl), N(C １ ~C ６ alkyl) ２ , NHC(O)(C １ ~C ６ alkyl), NHC(O)(C １ ~C ６ alkoxy), or C ６ ~C １０ Aryl, C ２ ~C ６ Alkenyl, C ２ ~C ６ Alkynyl, C ３ ~C １０ a group selected from the group consisting of C 6 -C 10 aryl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl, each of which optionally includes halo, C １ ~C ６ Alkyl, C １～６ Haloalkyl, C １ ~C ６ Alkoxy, oxo, N(C １ ~C ６ alkyl) ２ , N.H. ２ , NH(C １ ~C ６ substituted with one or more substituents independently selected from alkyl, hydroxy, and hydroxy; 【Chemistry 1-2】 but, 【Chemistry 1-3】 q is 0, 1, or 2; r is 0, 1, or 2; each of Y and Z is independently selected from C 1 -C 6 alkyl and hydroxy; or when two Ys are bonded to the same carbon, said two Ys, together with the carbons to which they are bonded, form a cyclopropyl ring; or when two Zs are bonded to the same carbon, said two Zs, together with the carbons to which they are bonded, form a cyclopropyl ring. provided that the compound of formula AA is 【Chemistry 1-4】 provided that the compound is not a compound selected from the group consisting of or a pharmaceutically acceptable salt thereof.

2. Formula AA 【Chemistry 2-1】 wherein m=0, 1, or 2; n=0, 1, or 2; During the ceremony, A is a 5-10 membered heteroaryl or C 6 -C 10 aryl; R 1 and R 2 are each independently C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halo, CN, NO 2 , CO 2 C 1 -C 6 alkyl, CO 2 C 3 -C 8 cycloalkyl, OCOC 1 -C 6 alkyl, OCOC 6 -C 10 aryl, OCO(5-10 membered heteroaryl), OCO(3-7 membered heterocycloalkyl), C 6 -C 10 aryl, 5-10 membered heteroaryl, NR 8 R 9 , C(O)R 13 , CONR 8 R 9 , SF 5 , SC 1 -C 6 alkyl, S(O 2 )C 1 -C 6 alkyl, S(O 2 )NR 11 R 12 , S(O)C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, and 3- to 7-membered heterocycloalkyl; wherein said C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 7 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, R 15 , NR 8 R 9 , ═NR 10 , COOC 1 -C 6 alkyl, CONR 8 R 9 , 3-7 membered heterocycloalkyl, C 6 -C 10 aryl, 5-10 membered heteroaryl, OCOC 1 -C 6 alkyl, OCOC 6 -C 10 aryl, OCO(5-10 membered heteroaryl), and OCO(3-7 membered heterocycloalkyl); each C 1 -C 6 alkyl substituent and each C 1 -C 6 alkoxy substituent of said R 1 or R 2 C 3 -C 7 cycloalkyl or said R 1 or R 2 3- to 7-membered heterocycloalkyl is further optionally and independently substituted with 1 to 3 hydroxy, —O(C 0 -C 3 alkylene)C 6 -C 10 aryl, halo, NR 8 R 9 , or oxo; each of said 3- to 7-membered heterocycloalkyl, C 6 -C 10 aryl, and 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, and OC 1 -C 6 alkyl; or a pair of R 1 and R 2 on adjacent atoms, taken together with the atom connecting them, independently form at least one monocyclic or bicyclic C 4 -C 12 carbocyclic ring or at least one monocyclic or bicyclic 5-12 membered heterocyclic ring: a) when each of said adjacent atoms is a carbon atom, said heterocycle contains from 1 to 3 heteroatoms and / or heteroatomic groups independently selected from O, NH, NR 13 , S, S(O), and S(O) 2 ; and b) when one or both of said adjacent atoms is a nitrogen atom, said heterocycle contains 0 to 2 heteroatoms and / or heteroatom groups independently selected from O, NH, NR 13 , S, S(O), and S(O) 2 (in addition to said nitrogen atom bonded to R 1 and / or R 2 ); and said carbocycle or heterocycle is optionally substituted with one or more substituents independently selected from hydroxy, halo, oxo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, OC 3 -C 10 cycloalkyl, NR 8 R 9 , ═NR 10 , CN, COOC 1 -C 6 alkyl, OS(O 2 )C 6 -C 10 aryl, S(O 2 )C 6 -C 10 aryl, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 10 cycloalkyl, 3-10 membered heterocycloalkyl, and CONR 8 R 9 ; wherein said C 1 -C 6 alkyl, C 1 -C 6 alkoxy, S(O 2 )C 6 -C 10 aryl, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 10 cycloalkyl, and 3-10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkoxy, oxo, NR 8 R 9 , ═NR 10 , COOC 1 -C 6 alkyl, C 6 -C 10 aryl, and CONR 8 R 9 ; R 10 is C 1 -C 6 alkyl; each of R 8 and R 9 at each occurrence is independently selected from hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 7 cycloalkyl, C 1 -C 6 haloalkyl, (C═NR 13 )NR 11 R 12 , S(O 2 )C 1 -C 6 alkyl, S(O 2 )NR 11 R 12 , COR 13 , CO 2 R 13 and CONR 11 R 12 ; said C 1 -C 6 alkyl is optionally substituted with one or more hydroxy, halo, C 1 -C 6 alkoxy, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 7 cycloalkyl, 3-7 membered heterocycloalkyl, or NR 11 R 12 ; or R 8 and R 9 together with the nitrogen to which they are attached form a 3-10 membered monocyclic or bicyclic ring optionally containing one or more heteroatoms in addition to the nitrogen to which they are attached, said ring being optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, oxo, N(C 1 -C 6 alkyl) 2 , NH 2 , NH(C 1 -C 6 alkyl), and hydroxy; R 13 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or -(Z 1 -Z 2 ) a1 -Z 3 ; Each of R 11 and R 12 at each occurrence is independently selected from hydrogen, C 1 -C 6 alkyl, and —(Z 1 -Z 2 ) a1 -Z 3 ; a1 is an integer selected from 0 to 10; each Z 1 is independently a C 1 -C 6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy; each Z 2 is independently a bond, NH, N(C 1 -C 6 alkyl), —O—, —S—, or 5- to 10-membered heteroarylene; Z 3 is independently C 6 -C 10 aryl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, C 1 -6 haloalkyl, C 1 -C 6 alkoxy, oxo, N(C 1 -C 6 alkyl) 2 , NH 2 , NH(C 1 -C 6 alkyl), and hydroxy; R 3 is hydrogen or methyl; R 15 is -(Z 4 -Z 5 ) a2 -Z 6 ; a2 is an integer selected from 1 to 10; each Z 4 is independently selected from —O—, —S—, —NH—, and —N(C 1 -C 3 alkyl)-; provided that the Z 4 group directly bonded to R 1 or R 2 is —O— or —S—; each Z 5 is independently a C 1 -C 6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy; and Z 6 is OH, OC 1 -C 6 alkyl, NH 2 , NH(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) 2 , NHC(O)(C 1 -C 6 alkyl), NHC(O)(C 1 -C 6 alkoxy), or a radical selected from the group consisting of C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl, wherein each of said C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl 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; 【Chemistry 2-2】 but, 【Chemistry 2-3】 R 7 is selected from C 1 -C 6 alkyl, C 6 -C 10 aryl, and C 3 -C 10 cycloalkyl; p is 0, 1, or 2; q is 0, 1, or 2; each Y is independently selected from C 1 -C 6 alkyl and hydroxy; or when two Ys are attached to the same carbon, the two Ys together with the carbons to which they are attached form a cyclopropyl ring. or a pharmaceutically acceptable salt thereof.

3. Formula AA 【Chemistry 3-1】 wherein m=0, 1, or 2; n=0, 1, or 2; During the ceremony, A is a 5-10 membered heteroaryl or C 6 -C 10 aryl; R 1 and R 2 are each independently C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halo, CN, NO 2 , CO 2 C 1 -C 6 alkyl, CO 2 C 3 -C 8 cycloalkyl, OCOC 1 -C 6 alkyl, OCOC 6 -C 10 aryl, OCO(5-10 membered heteroaryl), OCO(3-7 membered heterocycloalkyl), C 6 -C 10 aryl, 5-10 membered heteroaryl, NR 8 R 9 , C(O)R 13 , CONR 8 R 9 , SF 5 , SC 1 -C 6 alkyl, S(O 2 )C 1 -C 6 alkyl, S(O 2 )NR 11 R 12 , S(O)C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, and 3- to 7-membered heterocycloalkyl; wherein said C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 7 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, R 15 , NR 8 R 9 , ═NR 10 , COOC 1 -C 6 alkyl, CONR 8 R 9 , 3-7 membered heterocycloalkyl, C 6 -C 10 aryl, 5-10 membered heteroaryl, OCOC 1 -C 6 alkyl, OCOC 6 -C 10 aryl, OCO(5-10 membered heteroaryl), and OCO(3-7 membered heterocycloalkyl); each C 1 -C 6 alkyl substituent and each C 1 -C 6 alkoxy substituent of said R 1 or R 2 C 3 -C 7 cycloalkyl or said R 1 or R 2 3- to 7-membered heterocycloalkyl is further optionally and independently substituted with 1 to 3 hydroxy, —O(C 0 -C 3 alkylene)C 6 -C 10 aryl, halo, NR 8 R 9 , or oxo; each of said 3- to 7-membered heterocycloalkyl, C 6 -C 10 aryl, and 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, and OC 1 -C 6 alkyl; or a pair of R 1 and R 2 on adjacent atoms, taken together with the atom connecting them, independently form at least one monocyclic or bicyclic C 4 -C 12 carbocyclic ring or at least one monocyclic or bicyclic 5-12 membered heterocyclic ring: a) when each of said adjacent atoms is a carbon atom, said heterocycle contains from 1 to 3 heteroatoms and / or heteroatomic groups independently selected from O, NH, NR 13 , S, S(O), and S(O) 2 ; and b) when one or both of said adjacent atoms is a nitrogen atom, said heterocycle contains 0 to 2 heteroatoms and / or heteroatom groups independently selected from O, NH, NR 13 , S, S(O), and S(O) 2 (in addition to said nitrogen atom bonded to R 1 and / or R 2 ); and said carbocycle or heterocycle is optionally substituted with one or more substituents independently selected from hydroxy, halo, oxo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, OC 3 -C 10 cycloalkyl, NR 8 R 9 , ═NR 10 , CN, COOC 1 -C 6 alkyl, OS(O 2 )C 6 -C 10 aryl, S(O 2 )C 6 -C 10 aryl, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 10 cycloalkyl, 3-10 membered heterocycloalkyl, and CONR 8 R 9 ; wherein said C 1 -C 6 alkyl, C 1 -C 6 alkoxy, S(O 2 )C 6 -C 10 aryl, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 10 cycloalkyl, and 3-10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkoxy, oxo, NR 8 R 9 , ═NR 10 , COOC 1 -C 6 alkyl, C 6 -C 10 aryl, and CONR 8 R 9 ; R 10 is C 1 -C 6 alkyl; each of R 8 and R 9 at each occurrence is independently selected from hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 7 cycloalkyl, C 1 -C 6 haloalkyl, (C═NR 13 )NR 11 R 12 , S(O 2 )C 1 -C 6 alkyl, S(O 2 )NR 11 R 12 , COR 13 , CO 2 R 13 and CONR 11 R 12 ; said C 1 -C 6 alkyl is optionally substituted with one or more hydroxy, halo, C 1 -C 6 alkoxy, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 7 cycloalkyl, 3-7 membered heterocycloalkyl, or NR 11 R 12 ; or R 8 and R 9 together with the nitrogen to which they are attached form a 3-10 membered monocyclic or bicyclic ring optionally containing one or more heteroatoms in addition to the nitrogen to which they are attached, said ring being optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, oxo, N(C 1 -C 6 alkyl) 2 , NH 2 , NH(C 1 -C 6 alkyl), and hydroxy; R 13 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or -(Z 1 -Z 2 ) a1 -Z 3 ; Each of R 11 and R 12 at each occurrence is independently selected from hydrogen, C 1 -C 6 alkyl, and —(Z 1 -Z 2 ) a1 -Z 3 ; a1 is an integer selected from 0 to 10; each Z 1 is independently a C 1 -C 6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy; each Z 2 is independently a bond, NH, N(C 1 -C 6 alkyl), —O—, —S—, or 5- to 10-membered heteroarylene; Z 3 is independently C 6 -C 10 aryl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, C 1 -6 haloalkyl, C 1 -C 6 alkoxy, oxo, N(C 1 -C 6 alkyl) 2 , NH 2 , NH(C 1 -C 6 alkyl), and hydroxy; R 3 is hydrogen or methyl; R 15 is -(Z 4 -Z 5 ) a2 -Z 6 ; a2 is an integer selected from 1 to 10; each Z 4 is independently selected from —O—, —S—, —NH—, and —N(C 1 -C 3 alkyl)-; provided that the Z 4 group directly bonded to R 1 or R 2 is —O— or —S—; each Z 5 is independently a C 1 -C 6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy; and Z 6 is OH, OC 1 -C 6 alkyl, NH 2 , NH(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) 2 , NHC(O)(C 1 -C 6 alkyl), NHC(O)(C 1 -C 6 alkoxy), or a radical selected from the group consisting of C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl, wherein each of said C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl 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; 【Chemistry 3-2】 but, 【Chemistry 3-3】 each R 6 is independently selected from C 1 -C 6 alkyl; each R 7 is independently selected from halo; and p is 0 or 1; provided that the compound of formula AA is 【Chemistry 3-4】 provided that the compound is not a compound selected from the group consisting of or a pharmaceutically acceptable salt thereof.

4. Formula AA 【Chemistry 4-1】 wherein m=0, 1, or 2; n=0, 1, or 2; During the ceremony, A is a 5-10 membered heteroaryl or C 6 -C 10 aryl; R 1 and R 2 are each independently C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halo, CN, NO 2 , CO 2 C 1 -C 6 alkyl, CO 2 C 3 -C 8 cycloalkyl, OCOC 1 -C 6 alkyl, OCOC 6 -C 10 aryl, OCO(5-10 membered heteroaryl), OCO(3-7 membered heterocycloalkyl), C 6 -C 10 aryl, 5-10 membered heteroaryl, NR 8 R 9 , C(O)R 13 , CONR 8 R 9 , SF 5 , SC 1 -C 6 alkyl, S(O 2 )C 1 -C 6 alkyl, S(O 2 )NR 11 R 12 , S(O)C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, and 3- to 7-membered heterocycloalkyl; wherein said C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 7 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, R 15 , NR 8 R 9 , ═NR 10 , COOC 1 -C 6 alkyl, CONR 8 R 9 , 3-7 membered heterocycloalkyl, C 6 -C 10 aryl, 5-10 membered heteroaryl, OCOC 1 -C 6 alkyl, OCOC 6 -C 10 aryl, OCO(5-10 membered heteroaryl), and OCO(3-7 membered heterocycloalkyl); each C 1 -C 6 alkyl substituent and each C 1 -C 6 alkoxy substituent of said R 1 or R 2 C 3 -C 7 cycloalkyl or said R 1 or R 2 3- to 7-membered heterocycloalkyl is further optionally and independently substituted with 1 to 3 hydroxy, —O(C 0 -C 3 alkylene)C 6 -C 10 aryl, halo, NR 8 R 9 , or oxo; each of said 3- to 7-membered heterocycloalkyl, C 6 -C 10 aryl, and 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, and OC 1 -C 6 alkyl; or a pair of R 1 and R 2 on adjacent atoms, taken together with the atom connecting them, independently form at least one monocyclic or bicyclic C 4 -C 12 carbocyclic ring or at least one monocyclic or bicyclic 5-12 membered heterocyclic ring: a) when each of said adjacent atoms is a carbon atom, said heterocycle contains from 1 to 3 heteroatoms and / or heteroatomic groups independently selected from O, NH, NR 13 , S, S(O), and S(O) 2 ; and b) when one or both of said adjacent atoms is a nitrogen atom, said heterocycle contains 0 to 2 heteroatoms and / or heteroatom groups independently selected from O, NH, NR 13 , S, S(O), and S(O) 2 (in addition to said nitrogen atom bonded to R 1 and / or R 2 ); and said carbocycle or heterocycle is optionally substituted with one or more substituents independently selected from hydroxy, halo, oxo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, OC 3 -C 10 cycloalkyl, NR 8 R 9 , ═NR 10 , CN, COOC 1 -C 6 alkyl, OS(O 2 )C 6 -C 10 aryl, S(O 2 )C 6 -C 10 aryl, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 10 cycloalkyl, 3-10 membered heterocycloalkyl, and CONR 8 R 9 ; wherein said C 1 -C 6 alkyl, C 1 -C 6 alkoxy, S(O 2 )C 6 -C 10 aryl, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 10 cycloalkyl, and 3-10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkoxy, oxo, NR 8 R 9 , ═NR 10 , COOC 1 -C 6 alkyl, C 6 -C 10 aryl, and CONR 8 R 9 ; R 10 is C 1 -C 6 alkyl; each of R 8 and R 9 at each occurrence is independently selected from hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 7 cycloalkyl, C 1 -C 6 haloalkyl, (C═NR 13 )NR 11 R 12 , S(O 2 )C 1 -C 6 alkyl, S(O 2 )NR 11 R 12 , COR 13 , CO 2 R 13 and CONR 11 R 12 ; said C 1 -C 6 alkyl is optionally substituted with one or more hydroxy, halo, C 1 -C 6 alkoxy, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 7 cycloalkyl, 3-7 membered heterocycloalkyl, or NR 11 R 12 ; or R 8 and R 9 together with the nitrogen to which they are attached form a 3-10 membered monocyclic or bicyclic ring optionally containing one or more heteroatoms in addition to the nitrogen to which they are attached, said ring being optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, oxo, N(C 1 -C 6 alkyl) 2 , NH 2 , NH(C 1 -C 6 alkyl), and hydroxy; R 13 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or -(Z 1 -Z 2 ) a1 -Z 3 ; Each of R 11 and R 12 at each occurrence is independently selected from hydrogen, C 1 -C 6 alkyl, and —(Z 1 -Z 2 ) a1 -Z 3 ; a1 is an integer selected from 0 to 10; each Z 1 is independently a C 1 -C 6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy; each Z 2 is independently a bond, NH, N(C 1 -C 6 alkyl), —O—, —S—, or 5- to 10-membered heteroarylene; Z 3 is independently C 6 -C 10 aryl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, C 1 -6 haloalkyl, C 1 -C 6 alkoxy, oxo, N(C 1 -C 6 alkyl) 2 , NH 2 , NH(C 1 -C 6 alkyl), and hydroxy; R 3 is hydrogen or methyl; R 15 is -(Z 4 -Z 5 ) a2 -Z 6 ; a2 is an integer selected from 1 to 10; each Z 4 is independently selected from —O—, —S—, —NH—, and —N(C 1 -C 3 alkyl)-; provided that the Z 4 group directly bonded to R 1 or R 2 is —O— or —S—; each Z 5 is independently a C 1 -C 6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy; and Z 6 is OH, OC 1 -C 6 alkyl, NH 2 , NH(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) 2 , NHC(O)(C 1 -C 6 alkyl), NHC(O)(C 1 -C 6 alkoxy), or a radical selected from the group consisting of C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl, wherein each of said C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl 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; 【Chemistry 4-2】 but, 【Chemistry 4-3】 each R 6 is independently selected from C 1 -C 6 alkyl; each R 7 is independently selected from halo; and p is 0 or 1. or a pharmaceutically acceptable salt thereof.

5. Formula AA 【Chemistry 5-1】 wherein m=0, 1, or 2; n=0, 1, or 2; During the ceremony, A is a 5-10 membered heteroaryl or C 6 -C 10 aryl; R 1 and R 2 are each independently C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halo, CN, NO 2 , CO 2 C 1 -C 6 alkyl, CO 2 C 3 -C 8 cycloalkyl, OCOC 1 -C 6 alkyl, OCOC 6 -C 10 aryl, OCO(5-10 membered heteroaryl), OCO(3-7 membered heterocycloalkyl), C 6 -C 10 aryl, 5-10 membered heteroaryl, NR 8 R 9 , C(O)R 13 , CONR 8 R 9 , SF 5 , SC 1 -C 6 alkyl, S(O 2 )C 1 -C 6 alkyl, S(O 2 )NR 11 R 12 , S(O)C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, and 3- to 7-membered heterocycloalkyl; wherein said C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 7 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, CN, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, R 15 , NR 8 R 9 , ═NR 10 , COOC 1 -C 6 alkyl, CONR 8 R 9 , 3-7 membered heterocycloalkyl, C 6 -C 10 aryl, 5-10 membered heteroaryl, OCOC 1 -C 6 alkyl, OCOC 6 -C 10 aryl, OCO(5-10 membered heteroaryl), and OCO(3-7 membered heterocycloalkyl); each C 1 -C 6 alkyl substituent and each C 1 -C 6 alkoxy substituent of said R 1 or R 2 C 3 -C 7 cycloalkyl or said R 1 or R 2 3- to 7-membered heterocycloalkyl is further optionally and independently substituted with 1 to 3 hydroxy, —O(C 0 -C 3 alkylene)C 6 -C 10 aryl, halo, NR 8 R 9 , or oxo; each of said 3- to 7-membered heterocycloalkyl, C 6 -C 10 aryl, and 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, and OC 1 -C 6 alkyl; or a pair of R 1 and R 2 on adjacent atoms, taken together with the atom connecting them, independently form at least one monocyclic or bicyclic C 4 -C 12 carbocyclic ring or at least one monocyclic or bicyclic 5-12 membered heterocyclic ring: a) when each of said adjacent atoms is a carbon atom, said heterocycle contains from 1 to 3 heteroatoms and / or heteroatomic groups independently selected from O, NH, NR 13 , S, S(O), and S(O) 2 ; and b) when one or both of said adjacent atoms is a nitrogen atom, said heterocycle contains 0 to 2 heteroatoms and / or heteroatom groups independently selected from O, NH, NR 13 , S, S(O), and S(O) 2 (in addition to said nitrogen atom bonded to R 1 and / or R 2 ); and said carbocycle or heterocycle is optionally substituted with one or more substituents independently selected from hydroxy, halo, oxo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, OC 3 -C 10 cycloalkyl, NR 8 R 9 , ═NR 10 , CN, COOC 1 -C 6 alkyl, OS(O 2 )C 6 -C 10 aryl, S(O 2 )C 6 -C 10 aryl, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 10 cycloalkyl, 3-10 membered heterocycloalkyl, and CONR 8 R 9 ; wherein said C 1 -C 6 alkyl, C 1 -C 6 alkoxy, S(O 2 )C 6 -C 10 aryl, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 10 cycloalkyl, and 3-10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from hydroxy, halo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkoxy, oxo, NR 8 R 9 , ═NR 10 , COOC 1 -C 6 alkyl, C 6 -C 10 aryl, and CONR 8 R 9 ; R 10 is C 1 -C 6 alkyl; each of R 8 and R 9 at each occurrence is independently selected from hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 7 cycloalkyl, C 1 -C 6 haloalkyl, (C═NR 13 )NR 11 R 12 , S(O 2 )C 1 -C 6 alkyl, S(O 2 )NR 11 R 12 , COR 13 , CO 2 R 13 and CONR 11 R 12 ; said C 1 -C 6 alkyl is optionally substituted with one or more hydroxy, halo, C 1 -C 6 alkoxy, C 6 -C 10 aryl, 5-10 membered heteroaryl, C 3 -C 7 cycloalkyl, 3-7 membered heterocycloalkyl, or NR 11 R 12 ; or R 8 and R 9 together with the nitrogen to which they are attached form a 3-10 membered monocyclic or bicyclic ring optionally containing one or more heteroatoms in addition to the nitrogen to which they are attached, said ring being optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, oxo, N(C 1 -C 6 alkyl) 2 , NH 2 , NH(C 1 -C 6 alkyl), and hydroxy; R 13 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or -(Z 1 -Z 2 ) a1 -Z 3 ; Each of R 11 and R 12 at each occurrence is independently selected from hydrogen, C 1 -C 6 alkyl, and —(Z 1 -Z 2 ) a1 -Z 3 ; a1 is an integer selected from 0 to 10; each Z 1 is independently a C 1 -C 6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy; each Z 2 is independently a bond, NH, N(C 1 -C 6 alkyl), —O—, —S—, or 5- to 10-membered heteroarylene; Z 3 is independently C 6 -C 10 aryl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, C 1 -6 haloalkyl, C 1 -C 6 alkoxy, oxo, N(C 1 -C 6 alkyl) 2 , NH 2 , NH(C 1 -C 6 alkyl), and hydroxy; R 3 is hydrogen or methyl; R 15 is -(Z 4 -Z 5 ) a2 -Z 6 ; a2 is an integer selected from 1 to 10; each Z 4 is independently selected from —O—, —S—, —NH—, and —N(C 1 -C 3 alkyl)-; provided that the Z 4 group directly bonded to R 1 or R 2 is —O— or —S—; each Z 5 is independently a C 1 -C 6 alkylene optionally substituted with one or more substituents independently selected from oxo, halo, and hydroxy; and Z 6 is OH, OC 1 -C 6 alkyl, NH 2 , NH(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) 2 , NHC(O)(C 1 -C 6 alkyl), NHC(O)(C 1 -C 6 alkoxy), or a radical selected from the group consisting of C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl, wherein each of said C6-C10 aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl 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; 【Chemistry 5-2】 but, 【Chemistry 5-3】 R 6 is selected from C 1 -C 6 alkyl and C 3 -C 10 cycloalkyl; R 7 is selected from C 1 -C 6 alkyl, C 1 -C 6 haloalkyl and C 3 -C 10 cycloalkyl; or R 6 and R 7 together with the atom connecting them independently form a C 5 carbocycle optionally substituted with one or more C 1 -C 6 alkyl; q is 0, 1, or 2; each Y is independently selected from C 1 -C 6 alkyl; or when two Ys are attached to the same carbon, the two Ys, together with the carbons to which they are attached, form a cyclopropyl ring. or a pharmaceutically acceptable salt thereof.

6. R ３ The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

7. A is a 5-membered heteroaryl; or A is a 6- to 10-membered heteroaryl; or A is C ６ ~C １０ is aryl, The compound according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof.

8. A is thiophenyl, or A is thiazolyl, or A is pyrazolyl, or A is phenyl; The compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof.

9. R １ C optionally substituted with one or more hydroxy, if present １ ~C ６ alkyl, one or more halo, oxo, C １ ~C ６ Alkoxy or NR ８ R ９ C optionally substituted with １ ~C ６ Alkyl; one or more of hydroxy, halo, oxo, C １ ~C ６ Alkoxy, C １ ~C ６ Alkyl, or NR ８ R ９ C optionally substituted with ３ ~C ７ Cycloalkyl (wherein the C １ ~C ６ Alkoxy or C １ ~C ６ The alkyl may further optionally contain one to three hydroxy, halo, NR ８ R ９ or oxo); substituted with one or more of hydroxy, halo, oxo, C １ ~C ６ Alkyl, or NR ８ R ９ 3-7 membered heterocycloalkyl optionally substituted with １ ~C ６ Alkoxy or C １ ~C ６ The alkyl may further optionally contain one to three hydroxy, halo, NR ８ R ９ or oxo); C １ ~C ６ Haloalkyl; C １ ~C ６ Alkoxy; C １ ~C ６ Haloalkoxy; Halo; CN; CO-C １ ~C ６ Alkyl; CO-C ６ ~C １０ Aryl; CO(5-10 membered heteroaryl); CO ２ C １ ~C ６ Alkyl; CO ２ C ３ ~C ８ Cycloalkyl; OCOC １ ~C ６ Alkyl; OCOC ６ ~C １０ Aryl; OCO(5-10 membered heteroaryl); OCO(3-7 membered heterocycloalkyl); C ６ ~C １０ Aryl; 5- to 10-membered heteroaryl; NH ２ ; NHC １ ~C ６ Alkyl; N(C １ ~C ６ alkyl) ２ ;CONR ８ R ９ ;SF ５ ;S(O ２ ) NR １１ R １２ ;S(O)C １ ~C ６ alkyl; and S(O ２ ) C １ ~C ６ 9. The compound of any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, wherein each of the groups is independently selected from the group consisting of alkyl.

10. R １ 1-hydroxy-2-methylpropan-2-yl; 1,2-dihydroxy-2-propyl; methyl; ethyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolan-2-yl; COCH ３ ;COCH ２ CH ３ ; 2-Methoxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; 1-(dimethylamino)ethyl; Fluoro; Chloro; Phenyl; Pyridyl; Pyrazolyl; S(O ２ ) CH ３ and S(O ２ ) NR １１ R １２ The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

11. The following compounds: 【Table 1】 【Table 2】 【Table 3】 【Table 4】 【Table 5】 【Table 6】 【Table 7】 【Table 8】 【Table 9】 【Table 10】 【Table 11】 【Table 12】 【Table 13】 【Table 14】 【Table 15】 Table 16 Table 17 Table 18 【Table 19】 Table 20 Table 21 Table 22 Table 23 Table 24 Table 25 Table 26 Table 27 Table 28 Table 29 Table 30 Table 31 Table 32 Table 33 Table 34 Table 35 Table 36 Table 37 Table 38 Table 39 Table 40 Table 41 Table 42 Table 43 Table 44 Table 45 Table 46 Table 47 Table 48 Table 49 Table 50 Table 51 Table 52 Table 53 Table 54 Table 55 Table 56 Table 57 Table 58 Table 59 Table 60 Table 61 Table 62 Table 63 Table 64 Table 65 Table 66 Table 67 Table 68 Table 69 Table 70 Table 71 Table 72 Table 73 Table 74 Table 75 Table 76 Table 77 Table 78 Table 79 Table 80 Table 81 Table 82 Table 83 Table 84 Table 85 Table 86 Table 87 Table 88 Table 89 Table 90 【Table 91】 Table 92 Table 93 Table 94 【Table 95】 Table 96 Table 97 Table 98 【Table 99】 【Table 100】 Table 101 Table 102 Table 103 Table 104 Table 105 Table 106 Table 107 Table 108 Table 109 Table 110 Table 111 Table 112 Table 113 Table 114 Table 115 Table 116 Table 117 Table 118 Table 119 Table 120 Table 121 Table 122 Table 123 Table 124 Table 125 Table 126 Table 127 Table 128 Table 129 Table 130 Table 131 Table 132 Table 133 Table 134 Table 135 Table 136 Table 137 Table 138 Table 139 Table 140 Table 141 Table 142 Table 143 Table 144 Table 145 Table 146 Table 147 Table 148 Table 149 Table 150 Table 151 Table 152 Table 153 Table 154 or a pharmaceutically acceptable salt thereof.

12. A compound of the formula: Table 155 or a pharmaceutically acceptable salt thereof.

13. A compound of the formula: Table 156 or a pharmaceutically acceptable salt thereof.

14. Part S (=O) (NHR ３ 14. The compound of claim 1, wherein the sulfur in ═N— has the (S) stereochemistry, or a pharmaceutically acceptable salt thereof.

15. Part S (=O) (NHR ３ 14. The compound of any one of claims 1 to 13, wherein the sulfur in )=N- has the (R) stereochemistry, or a pharmaceutically acceptable salt thereof.

16. A pharmaceutical composition comprising a compound according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.

17. 17. The pharmaceutical composition of claim 16 for use in treating a subject having a disease in which NLRP3 signaling contributes to the pathology and / or symptoms, and / or progression of the disease.

18. The use, a metabolic disorder, optionally wherein said metabolic disorder is type 2 diabetes, atherosclerosis, obesity or gout; a disease of the central nervous system, optionally wherein said disease of the central nervous system is Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, or Parkinson's disease; a pulmonary disease, optionally wherein the pulmonary disease is asthma, COPD, or idiopathic pulmonary fibrosis; liver disease, optionally wherein said liver disease is NASH syndrome, viral hepatitis or cirrhosis; a pancreatic disease, optionally wherein said pancreatic disease is acute pancreatitis or chronic pancreatitis; a kidney disease, optionally wherein the kidney disease is acute kidney injury or chronic kidney injury; a bowel disease, optionally wherein the bowel disease is Crohn's disease or ulcerative colitis; a skin disease, optionally wherein said skin disease is psoriasis; a musculoskeletal disorder, optionally wherein the musculoskeletal disorder is scleroderma; a vascular disorder, optionally wherein said vascular disorder is giant cell arteritis; a bone disorder, optionally wherein said bone disorder is osteoarthritis, osteoporosis or osteopetrosis; an ocular disease, optionally wherein the ocular disease is glaucoma or macular degeneration; a disease caused by a viral infection, optionally wherein said disease caused by a viral infection is HIV or AIDS; an autoimmune disease, optionally wherein the autoimmune disease is rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroiditis, cancer, and aging, and optionally wherein the disease or condition is cancer is selected from myelodysplastic syndrome (MDS); non-small cell lung cancer, such as non-small cell lung cancer in patients with NLRP3 mutations or overexpression; acute lymphoblastic leukemia (ALL), such as ALL in patients resistant to glucocorticoid treatment; Langerhans cell histiocytosis (LCH); multiple myeloma; promyelocytic leukemia; acute myeloid leukemia (AML), chronic myeloid leukemia (CML); gastric cancer; and lung cancer metastasis; 18. The pharmaceutical composition of claim 17, for the treatment of a disease, disorder or condition which is any one of:

19. 19. The pharmaceutical composition according to claim 17 or 18, said use comprising administering to said subject a therapeutically effective amount of an anti-TNFα agent; optionally, an NLRP3 antagonist is administered to the subject prior to administration of the anti-TNFα agent to the subject; or the anti-TNFα agent is administered to the subject prior to administration of the NLRP3 antagonist to the subject; or The pharmaceutical composition, wherein the NLRP3 antagonist and the anti-TNFα agent are administered to the subject substantially simultaneously.

20. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein a1 is an integer selected from 0 to 5.

21. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein a2 is an integer selected from 1 to 5.

22. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein a2 is an integer selected from 2 to 5.

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