Granted Patent B2

US 12,421,196 · App. 18/353,410 · Granted Sep 23, 2025

Inventors: George Hartman (Lansdale, PA); Paul Humphries (Menlo Park, CA); Kevin Edward Leif Wilhelmsen (Albany, CA)

Assignee: BioAge Labs, Inc.

C07D231/56A61K31/4353A61K31/437C07D235/06C07D401/12C07D403/12C07D405/12C07D413/12C07D417/12C07D471/04

Abstract

Claims (68)

1. A method of inhibiting NLRP3 inflammasome 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, wherein alkyl and cycloalkyl are each optionally substituted with R 6 ;

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 is 0 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 optionally substituted with C 1-6 alkyl.

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 1 , 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:

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 a compound of Formula VI:

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, 5-6 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 C is pyridinyl;

R 1 is selected from the group consisting of H, C 1-6 alkyl, and C 3-6 cycloalkyl, wherein alkyl and cycloalkyl are each optionally substituted with R 6 ;

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, —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, —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, —OC 1-6 alkyl, halo, —CN, —OH, —NH 2 , —NH(C 1-6 alkyl), and —N(C 1-6 alkyl) 2 ;

m is 0, 1, or 2;

n is 1 or 2; and

p is 0, 1, or 2.

15. The method of claim 14 , wherein the compound of Formula VI is a compound of Formula VIa:

or a pharmaceutically acceptable salt thereof.

16. The method of claim 14 , wherein the compound of Formula VI is a compound of Formula VIb:

or a pharmaceutically acceptable salt thereof.

17. The method of claim 14 , wherein the compound of Formula VI is a compound of Formula VIc:

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

Assignments (1)

Continuity (4)

References Cited (31)