COMPOUNDS FOR INHIBITING NLRP3 AND USES THEREOF

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

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

each R 2a is hydrogen;

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 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, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, 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;

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.

2 . The compound of claim 1 , 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 .

3 . The compound of claim 2 , 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 .

4 . The compound of claim 3 , wherein R 4 is a bond.

5 . The compound of claim 3 , wherein R 5 is hydrogen or C 1 -C 6 alkyl.

6 . The compound of claim 1 , wherein R 1 is —(CH 2 ) n -(3- to 8-membered heterocycloalkyl).

7 . The compound of claim 6 , wherein heterocycloalkyl is substituted with one or more halo, C 1 -C 6 alkyl, or —R 4 OR 5 .

8 . The compound of claim 6 , wherein n is an integer selected from 0 or 1.

9 . The compound of claim 1 , wherein R 1 is —(CH 2 ) n —(C 3 -C 10 cycloalkyl).

10 . The compound of claim 9 , wherein the cycloalkyl is substituted with one or more halo, C 1 -C 6 alkyl, or —R 4 OR 5 .

11 . The compound of claim 1 , wherein Y is C 6 -C 10 aryl.

12 . The compound of claim 11 , wherein Y is phenyl.

13 . The compound of claim 12 , wherein the phenyl is substituted with one or more halo, C 1 -C 6 alkyl, or —R 4 OR 5 .

14 . The compound of claim 1 , selecting from

15 . The compound of claim 14 , selecting from

5-chloro-2-(4-((2-hydroxy-2-methylpropyl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol;

5-chloro-2-(4-((2-methoxy-2-methylpropyl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol;

5-methoxy-2-(4-((2-methoxy-2-methylpropyl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol;

2-(4-((2-methoxy-2-methylpropyl)amino)pyrido[3,4-d]pyridazin-1-yl)-5-(trifluoromethoxy) phenol;

(S)-5-chloro-2-(4-((tetrahydrofuran-3-yl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol;

(S)-5-chloro-2-(4-(((3,3-difluorocyclopentyl)methyl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol;

(R)-5-chloro-2-(4-(((3-fluorotetrahydrofuran-3-yl)methyl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol;

5-chloro-2-(4-((2-(methoxy-d3)-2-methylpropyl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol;

5-chloro-2-(4-((oxazol-4-ylmethyl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol; and

5-chloro-2-(4-((4-fluorobenzyl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol.

16 . The compound of claim 15 , selecting from

5-chloro-2-(4-((2-hydroxy-2-methylpropyl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol;

5-methoxy-2-(4-((2-methoxy-2-methylpropyl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol;

(S)-5-chloro-2-(4-((tetrahydrofuran-3-yl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol;

5-chloro-2-(4-((oxazol-4-ylmethyl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol; and

5-chloro-2-(4-((4-fluorobenzyl)amino)pyrido[3,4-d]pyridazin-1-yl)phenol.

17 . A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.

18 . A pharmaceutical composition comprising a compound of claim 14 , and a pharmaceutically acceptable carrier.

19 . A pharmaceutical composition comprising a compound of claim 15 , and a pharmaceutically acceptable carrier.

20 . A pharmaceutical composition comprising a compound of claim 16 , and a pharmaceutically acceptable carrier.