Compounds and compositions for treating conditions associated with NLRP activity

1. A compound of Formula AA

wherein

o=1 or 2;

p=0, 1, 2, or 3;

Y is —CR 15 R 15 — or —NR 16 —;

ring A is:

(i) a saturated or unsaturated monocyclic ring that includes from 5-8 ring atoms (inclusive of N—R 3 and S(O)); or

(ii) a saturated or unsaturated bicyclic or tricyclic ring that includes from 8-20 ring atoms (inclusive of N—R 3 and S(O)),

wherein the dotted, circular line connecting N—R 3 and S is a divalent group that includes from 3-6 ring atoms; wherein:

(a) from 0-2 of the divalent group's ring atoms are ring heteroatoms, which are each independently selected from the group consisting of O, N, NH, NR 13 , S, S(O), and S(O) 2 ; and

(b) from 1-6 of the divalent group's ring atoms are ring carbon atoms, which are each independently selected from the group consisting of C, CH, CH 2 , C(O), CR 1 , C(R 1 ) 2 , and CHR 1 ;

wherein:

(1) when ring A is a monocyclic ring, then each of the divalent group's 1-6 ring carbon atoms is independently selected from the group consisting of CH, CH 2 , C(O), CR 1 , C(R 1 ) 2 , and CHR 1 ; and

(2) when ring A is a bicyclic or tricyclic ring, then (A) or (B) applies:

(A) two or three adjacent ring carbon atoms of the divalent group are each independently selected from the group consisting of C, CH, and CR 1 , and are fused to a second ring that is selected from the group consisting of:

(a) C 6-10 aryl optionally substituted with from 1-5 independently selected R a ;

(b) heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are each independently selected from the group consisting of N, N(R N ), O, and S, wherein the heteroaryl is optionally substituted with from 1-3 independently selected R a ;

(c) C 3-10 cycloalkyl optionally substituted with from 1-4 independently selected R b ;

(d) heterocycloalkyl including from 3-10 ring atoms, wherein from 1-3 ring atoms are each independently selected from the group consisting of N(R N ), O, and S, wherein the heterocycloalkyl is optionally substituted with from 1-4 independently selected R b ; or

(B) one of the divalent group's ring carbon atoms is C and is spiro-fused to a second ring that is selected from the group consisting of:

(a) C 3-10 cycloalkyl optionally substituted with from 1-4 independently selected R b ;

(b) heterocycloalkyl including from 3-10 ring atoms, wherein from 1-3 ring atoms are each independently selected from the group consisting of N(R N ), O, and S, wherein the heterocycloalkyl is optionally substituted with from 1-4 independently selected R b ;

each R 1 is independently selected from the group consisting of: C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halo, CN, NO 2 , COC 1 -C 6 alkyl, CO—C 6 -C 10 aryl, CO(5- to 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- to 10-membered heteroaryl), OCO(3- to 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 , NHCOC 1 -C 6 alkyl, NHCOC 6 -C 10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), NHCOC 2 -C 6 alkynyl, NHCOOC 1 -C 6 alkyl, NH—(C═NR 13 )NR 11 R 12 , CONR 8 R 9 , SF 5 , SC 1 -C 6 alkyl, S(O 2 )C 1 -C 6 alkyl, S(O)C 1 -C 6 alkyl, S(O 2 )NR 11 R 12 , C 3 -C 7 cycloalkyl, and 3- to 7-membered heterocycloalkyl,

wherein the C 1 -C 6 alkyl, C 6 -C 10 aryl, 5- to 10-membered heteroaryl, C 1 -C 6 haloalkyl, C 3 -C 7 cycloalkyl, and 3- to 7-membered heterocycloalkyl is 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, NR 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 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), NHCOC 1 -C 6 alkyl, NHCOC 6 -C 10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC 2 -C 6 alkynyl;

wherein when R 1 is C 3 -C 7 cycloalkyl, 3- to 7-membered heterocycloalkyl, C 6 -C 10 aryl, or 5- to 10-membered heteroaryl, each C 1 -C 6 alkyl substituent and each C 1 -C 6 alkoxy substituent on R 1 , when present, is further optionally independently substituted with one to three hydroxy, C 1 -C 6 alkoxy, halo, NR 8 R 9 , or oxo;

wherein the 3- to 7-membered heterocycloalkyl, C 6 -C 10 aryl, 5- to 10-membered heteroaryl, NHCOC 6 -C 10 aryl, NHCO(5- to 10-membered heteroaryl) and NHCO(3- to 7-membered heterocycloalkyl) substituents on R 1 are optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, and OC 1 -C 6 alkyl;

each R a is independently selected from hydroxy, halo, 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, OC 6 -C 10 aryl, 5- to 10-membered heteroaryl, C 3 -C 10 cycloalkyl, 3-to 10-membered heterocycloalkyl, CO 2 H, and CONR 8 R 9 ,

wherein the 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 one or more substituents each independently selected from hydroxy, halo, C 1 -C 6 alkyl, C 1-4 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl, C 1 -C 6 alkoxy, oxo, NR 8 R 9 , ═NR 10 , COOC 1 -C 6 alkyl, C 6 -C 10 aryl, CO 2 H, and CONR 8 R 9 ,

each R b is 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, OC 6 -C 10 aryl, 5- to 10-membered heteroaryl, C 3 -C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl, CO 2 H, and CONR 8 R 9 ,

wherein the 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 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, CO 2 H, and CONR 8 R 9 ;

each R N is independently selected from hydrogen, C 1 -C 6 alkyl, (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 ;

wherein the 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- to 10-membered heteroaryl, C 3 -C 7 cycloalkyl, or 3- to 7-membered heterocycloalkyl;

ring B is a 5-10-membered heteroaryl or a C 6 -C 10 aryl;

R 6 and R 7 are each independently selected from C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halo, CN, NO 2 , COC 1 -C 6 alkyl, 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- to 10-membered heteroaryl), OCO(3- to 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 )C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl and 3- to 10-membered heterocycloalkyl, and a C 2 -C 6 alkenyl,

wherein R 6 and R 7 are each optionally substituted with one or more substituents independently selected from hydroxy, halo, CN, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, NR 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 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), NHCOC 1 -C 6 alkyl, NHCOC 6 -C 10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), NHCOC 2 -C 6 alkynyl, C 6 -C 10 aryloxy, and S(O 2 )C 1 -C 6 alkyl; and wherein the C 1 -C 6 alkyl or C 1 -C 6 alkoxy that R 6 or R 7 is substituted with is optionally substituted with one or more hydroxyl, C 6 -C 10 aryl or NR 8 R 9 ;

wherein the 3- to 7-membered heterocycloalkyl, C 6 -C 10 aryl, 5- to 10-membered heteroaryl, NHCOC 6 -C 10 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, C 1 -C 6 alkyl, and OC 1 -C 6 alkyl;

OR

at least one pair of R 6 and R 7 on adjacent carbon atoms taken together with the carbon atoms to which each is attached form a C 4 -C 8 carbocyclic ring or a 5- to 8-membered heterocyclic ring containing 1-3 heteroatoms and/or heteroatomic groups independently selected from O, N, NH, NR 13 , S, S(O), and S(O) 2 , wherein the carbocyclic ring or heterocyclic ring is optionally substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halo, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, NR 8 R 9 , CH 2 NR 8 R 9 , ═NR 10 , COOC 1 -C 6 alkyl, C 6 -C 10 aryl, and CONR 8 R 9 ,

each occurrence of R 8 and R 9 is independently selected from hydrogen, C 1 -C 6 alkyl, (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 ;

wherein the 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- to 10-membered heteroaryl, C 3 -C 7 cycloalkyl, or 3- to 7-membered heterocycloalkyl; or R 8 and R 9 taken together with the nitrogen atom to which each is attached form a 3- to 7-membered ring optionally containing one or more additional heteroatoms;

R 10 is C 1 -C 6 alkyl;

R 13 is C 1 -C 6 alkyl, C 6 -C 10 aryl, or 5- to 10-membered heteroaryl;

each of R 11 and R 12 at each occurrence is independently selected from hydrogen and C 1 -C 6 alkyl;

R 3 is selected from hydrogen, cyano, hydroxy, C 1 -C 6 alkoxy, C 1 -C 6 alkyl, and

wherein the C 1 -C 2 alkylene group is optionally substituted by oxo;

R 14 is hydrogen, C 1 -C 6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl or C 6 -C 10 monocyclic or bicyclic aryl, wherein each C 1 -C 6 alkyl, aryl, or heteroaryl is optionally independently substituted with 1 or 2 R 6 ;

each occurrence of R 15 is independently selected from hydrogen and C 1 -C 6 alkyl; and

R 16 is selected from hydrogen and C 1 -C 6 alkyl;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein ring A has Formula (A1):

wherein:

represents a single bond or a double bond;

ring C is selected from the group consisting of:

(a) C 6-10 aryl optionally substituted with from 1-5 independently selected R a ;

(b) heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are each independently selected from the group consisting of N, N(R N ), O, and S, wherein the heteroaryl is optionally substituted with from 1-3 independently selected R a ;

(c) C 3-10 cycloalkyl optionally substituted with from 1-4 independently selected R b ; and

(d) heterocycloalkyl including from 3-10 ring atoms, wherein from 1-3 ring atoms are each independently selected from the group consisting of N(R N ), O, and S, wherein the heterocycloalkyl is optionally substituted with from 1-4 independently selected R b ; and

each of A 1a and A 1c is independently selected from: a bond, CH 2 , CHR 1 , C(R 1 ) 2 , C(O), N, NH, NR 13 , O, S(O) 2 , and A 1d -A 1e -A 1f ;

provided that one or more of A 1a and A 1c is other than a bond;

wherein each of A 1d , A 1e , and A 1f is independently a bond, CH 2 , CHR 1 , C(R 1 ) 2 , C(O), S(O) 2 , NH, NR 13 , and O, provided that from 2-3 of A 1d , A 1e , and A 1f are other than a bond,

and provided that A 1d and A 1e are not both O or not both S(O) 2 , and A 1e and A 1f are not both O or not both S(O) 2 .

3. The compound of claim 2 , wherein ring A is selected from:

4. The compound of claim 2 , wherein each R 1 when present is independently selected from the group consisting of: C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halo, CN, C 6 -C 10 aryl, 5- to 10-membered heteroaryl, NH 2 , NHC 1 -C 6 alkyl, N(C 1 -C 6 alkyl) 2 , NHCOC 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, and 3- to 7-membered heterocycloalkyl.

5. The compound of claim 2 , wherein ring Cis selected from the group consisting of:

C 6 aryl optionally substituted with from 1-3 independently selected R a ;

heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are each independently selected from the group consisting of N, N(R N ), O, and S, wherein the heteroaryl is optionally substituted with from 1-3 independently selected R a ;

thiophenyl optionally substituted with from 1-2 independently selected R a ;

heteroaryl including from 8-10 ring atoms, wherein from 1-3 ring atoms are each independently selected from the group consisting of N, N(R N ), O, and S, wherein the heteroaryl is optionally substituted with from 1-2 independently selected R a ;

C 3-10 cycloalkyl optionally substituted with from 1-4 independently selected R b ; and

heterocycloalkyl including from 3-10 ring atoms, wherein from 1-3 ring atoms are each independently selected from the group consisting of N(R N ), O, and S, wherein the heterocycloalkyl is optionally substituted with from 1-4 independently selected R b .

6. The compound of claim 1 , wherein ring A has Formula (A2):

wherein ring D is selected from the group consisting of:

(a) C 3-10 cycloalkyl optionally substituted with from 1-4 independently selected R b ; and

(b) heterocycloalkyl including from 3-10 ring atoms, wherein from 1-3 ring atoms are each independently selected from the group consisting of N(R N ), O, and S, wherein the heterocycloalkyl is optionally substituted with from 1-4 independently selected R b ; and

each of A 2a , A 2b , A 2c , and A 2d is independently selected from: a bond, NH, NR 13 , O, CH 2 , CH(R 1 ), C(R 1 ) 2 , C(O), and S(O) 2 ; provided that one or more of A 2a , A 2b , A 2c , and A 2d are other than a bond, and

provided that A 2c and A 2d are not both O or not both S(O) 2 ; and A 2a and A 2b are not both O or not both S(O) 2 .

7. The compound of claim 1 , wherein ring A is selected from the group consisting of

8. The compound of claim 7 , wherein each R 1 is independently selected from the group consisting of: C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halo, CN, COC 1 -C 6 alkyl, CO 2 C 1 -C 6 alkyl, CO 2 C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 5- to 10-membered heteroaryl, NH 2 , NHC 1 -C 6 alkyl, N(C 1 -C 6 alkyl) 2 , NHCOC 1 -C 6 alkyl, NHCOC 6 -C 10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), NHCOC 2 -C 6 alkynyl, CONR 8 R 9 , S(O 2 )C 1 -C 6 alkyl, S(O)C 1 -C 6 alkyl, S(O 2 )NR 11 R 12 , C 3 -C 7 cycloalkyl, and 3- to 7-membered heterocycloalkyl, wherein the C 1 -C 6 alkyl, C 6 -C 10 aryl, C 1 -C 6 haloalkyl, C 3 -C 7 cycloalkyl, and 3- to 7-membered heterocycloalkyl is 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, NR 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 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), NHCOC 1 -C 6 alkyl, NHCOC 6 -C 10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC 2 -C 6 alkynyl;

wherein when R 1 is C 3 -C 7 cycloalkyl, 3- to 7-membered heterocycloalkyl, C 6 -C 10 aryl, or 5- to 10-membered heteroaryl, each C 1 -C 6 alkyl substituent and each C 1 -C 6 alkoxy substituent on R 1 , when present, is further optionally independently substituted with one to three hydroxy, C 1 -C 6 alkoxy, halo, NR 8 R 9 , or oxo; and

wherein the 3- to 7-membered heterocycloalkyl, C 6 -C 10 aryl, 5- to 10-membered heteroaryl, NHCOC 6 -C 10 aryl, NHCO(5- to 10-membered heteroaryl) and NHCO(3- to 7-membered heterocycloalkyl) substituents on R 1 are optionally substituted with one or more substituents independently selected from halo, C 1 -C 6 alkyl, and OC 1 -C 6 alkyl.

9. The compound of claim 1 , wherein Bis

and

wherein each R 6 is independently selected from C 1 -C 6 alkyl,

C 3 -C 7 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halo, CN, C 6 -C 10 aryl, 5- to 10-membered heteroaryl, CO—C 1 -C 6 alkyl; CONR 8 R 9 , and 4- to 6-membered heterocycloalkyl,

wherein the C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 7 cycloalkyl and 4- to 6-membered heterocycloalkyl is 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, NR 8 R 9 , —NR 10 , COOC 1 -C 6 alkyl, CONR 8 R 9 , 4- to 6-membered heterocycloalkyl, C 6 -C 10 aryl, 5- to 10-membered heteroaryl, OCOC 1 -C 6 alkyl, OCOC 6 -C 10 aryl, OCO(5- to 10-membered heteroaryl), OCO(4- to 6-membered heterocycloalkyl), NHCOC 1 -C 6 alkyl, NHCOC 6 -C 10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(4- to 6-membered heterocycloalkyl), and NHCOC 2 -C 6 alkynyl;

wherein R 7 is independently selected from C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halo, CN, COC 1 -C 6 alkyl, CO 2 C 1 -C 6 alkyl, CO 2 C 3 -C 6 cycloalkyl, OCOC 1 -C 6 alkyl, OCOC 6 -C 10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), C 6 -C 10 aryl, 5- to 10-membered heteroaryl, CONR 8 R 9 , SF 5 , S(O 2 )C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl and 4- to 6-membered heterocycloalkyl, wherein the C 1 -C 6 alkyl is optionally substituted with one to two C 1 -C 6 alkoxy.

10. The compound of claim 1 , wherein R 3 is hydrogen, and Y is —CR 15 R 15 or NR 16 .

11. The compound of claim 1 , wherein the compound has Formula AA-1:

wherein:

A 1c is C(O) or CH 2 ;

ring C is selected from the group consisting of:

(a) C 6-10 aryl optionally substituted with from 1-5 independently selected R a ; and

(b) heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are each independently selected from the group consisting of N, N(R N ), O, and S, wherein the heteroaryl is optionally substituted with from 1-3 independently selected R a ; and

R 3 , ring B, Y, R 6 , R 7 , o, and p are as defined in claim 1 .

12. The compound of claim 11 , wherein A 1c is C(O) and ring C is C 6 aryl optionally substituted with from 1-2 independently selected R a .

13. The compound of claim 1 , wherein the compound has Formula AA-2:

wherein:

A 3a is C(O) or CH 2 ;

A 3b is CH 2 , CHR 1 , or C(R 2 ) 2 ;

A 3c is CH 2 , CHR 1 , or C(R 2 ) 2 ;

A 3d is a bond or CH 2 ; and

each of R 3 , Y, ring B, R 6 , R 7 , o, and p are as defined in claim 1 .

14. The compound of claim 13 , wherein B is

and wherein each R 6 and R 7 is independently selected from C 1 -C 6 alkyl optionally substituted with hydroxy, C 3 -C 7 cycloalkyl, C 1 -C 6 haloalkyl, and halo;

or at least one pair of R 6 and R 7 on adjacent atoms, taken together with the atoms connecting them, independently form a C 4 -C 8 carbocyclic ring or a 5-membered heterocyclic ring containing 1 O, wherein the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from C 1 -C 6 alkyl.

15. The compound of claim 14 , wherein R 3 is H and Y is NH.

16. A compound selected from the group consisting of the compounds in Tables below or pharmaceutically acceptable salts thereof:

Cmpd

#

Structure

101

102

103

104

105

106

106a

106b

107

107a

107b

108

108a

108b

109

110

111

112

112a

112b

113

114

115

116

116a

116b

117

118

119

119a

119b

120

121

121a

121b

122

123

123a

123b

124

124a

124b

125

126

127

127a

127b

128

129

129a

129b

130

130a

130b

131

131a

131b

Cmpd

#

Structure

201

202

203

204

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

220

221

222

223

224

225

226

227

228

229

230

231

232

233

234

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

251

252

253

254

255

256

257

258

259

260

261

262

263

264

265

266

267

268

269

270

271

272

273

274

275

276

277

278

279

280

281

282

283

284

285

286

Cmpd

#

Structure

102a

102b

103a

103b

104a

113a

115a

132

132a

132b

133

133a

133b

134

134a

134b

135

136

137

138

139a

139b

204

207

208

208a

208b

209

211

211a

211b

213

214

216

217

218

223

223a

223b

229

249a

17. A pharmaceutical composition comprising a compound or salt as claimed in claim 1 and one or more pharmaceutically acceptable excipients.

18. A method for modulating NLRP3 activity, the method comprising contacting a subject with an effective amount of a compound as claimed in claim 1 .

19. The method of claim 18 , wherein the modulating comprises antagonizing NLRP3, in vivo, and the subject is a human.

20. The method of claim 19 , further comprising administering a therapeutically effective amount of an anti-TNFα agent to the subject.