Inhibitors of NLRP3 inflammasome

1 . A method of treating inflammaging in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of Formula VII:

or a pharmaceutically acceptable salt thereof, wherein

X, Y, and Z, together with the ring to which they are attached, form

Ring A is selected from the group consisting of C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl, and 4-10 membered heterocycloalkyl;

Ring B is selected from the group consisting of phenyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, and 3-6 membered heterocycloalkyl;

alternatively, Ring B is absent and m is 0;

Ring D is pyridinyl;

R 1 is selected from the group consisting of H, C 1-6 alkyl, and C 3-6 cycloalkyl,

R 2 and R 3 are each independently selected from the group consisting of H, C 1-6 alkyl, C 3-6 cycloalkyl, and 3-6 membered heterocycloalkyl;

each R 4 is independently selected from the group consisting of C 1-6 alkyl, halo, —OH, —OR 6 , C 3-7 cycloalkyl, 3-7 membered heterocycloalkyl, and —COR 6 ;

each R 5 is independently selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, halo, —CN, —COR 6 , and —SO 2 R 6 ;

each R 6 is independently selected from the group consisting of C 1-6 alkyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, —NH 2 , —NH(C 1-6 alkyl), and —N(C 1-6 alkyl) 2 ;

each R 9 is independently selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkyl-OH, —OC 1-6 alkyl, C 1-6 alkyl-O—C 1-6 alkyl, O(C 3-6 cycloalkyl), halo, —CN, —OH, —NH 2 , —NH(C 1-6 alkyl), and —N(C 1-6 alkyl) 2 ;

m is 0, 1, 2, or 3;

n is 0, 1, 2, or 3; and

p is 0, 1, 2, or 3.

2 . The method of claim 1 , wherein the compound of Formula VII is selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

3 . The method of claim 1 , wherein the compound of Formula VII is administered in a pharmaceutical composition comprising the compound, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

4 . The method of claim 1 , wherein

Ring A is phenyl or 5-6 membered heteroaryl;

Ring B is phenyl or 5-6 membered heteroaryl;

Ring D is pyridinyl;

R 1 is H or C 1-3 alkyl;

R 2 and R 3 are each independently selected from the group consisting of H and C 1-3 alkyl;

each R 4 is independently selected from the group consisting of halo, —OR 6 C 3-7 cycloalkyl, and —COR 6 ;

each R 5 is independently selected from the group consisting of C 1-3 haloalkyl, halo, —CN, and —COR 6 ;

each R 6 is independently selected from the group consisting of C 1-6 alkyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and —NH(C 1-3 alkyl);

each R 9 is independently selected from the group consisting of C 1-6 alkyl, C 1-3 haloalkyl, C 1-3 alkyl-OH, —OC 1-3 alkyl, O(C 3-6 cycloalkyl), and —CN;

m is 0, 1, or 2;

n is 0, 1, or 2; and

p is0 or 1.

5 . The method of claim 1 , wherein Ring A is selected from the group consisting of phenyl, pyridinyl, pyrimidinyl, and pyrazinyl.

6 . The method of claim 1 , wherein Ring B is selected from phenyl and 5-6 membered heteroaryl.

7 . The method of claim 1 , wherein R 1 is C 1-6 alkyl or C 3-6 cycloalkyl.

8 . The method of claim 1 , wherein R 2 and R 3 are each independently selected from the group consisting of H and C 1-3 alkyl.

9 . The method of claim 1 , wherein R 4 is —OC 1-6 alkyl.

10 . The method of claim 3 , wherein R 5 is selected from the group consisting of C 1-6 haloalkyl, halo, —CN, —CONH 2 , and —CONH(C 1-6 alkyl).

11 . The method of claim 1 , wherein each R 9 is independently selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkyl-OH, —OC 1-6 alkyl, O(C 3 cycloalkyl), and —CN.

12 . The method of claim 1 , wherein the compound of Formula VII is selected from the group consisting of:

and

or a pharmaceutically acceptable salt thereof.

13 . The method of claim 1 , wherein the compound of Formula VII is

or a pharmaceutically acceptable salt thereof.

14 . The method of claim 1 , wherein the compound of Formula VII is

or a pharmaceutically acceptable salt thereof.