Granted Patent B2

US 12,404,265 · App. 18/019,452 · Granted Sep 2, 2025

Inventors: Jennifer Aiden Kozak (Pacifica, CA); Sean Pomeroy Brown (Half Moon Bay, CA); Christopher Michael Tegley (San Carlos, CA); Alexander Wayne Schammel (San Francisco, CA); Liusheng Zhu (Foster City, CA); Maximiliano De La Higuera Macias (San Francisco, CA); Shilpa Sambashivan (Los Altos, CA)

Assignee: NURA BIO, INC.

C07D403/14A61P25/28C07D403/04

Abstract

Claims (51)

1. A compound of Formula Ia:

or a pharmaceutically acceptable salt thereof, wherein:

A is N or N + —O − ;

W is O, S, or NR N ;

---- is a single, double, or triple bond;

wherein when the ---- bond between X and Y is a single bond, then:

X is CR 5 R 6 and Y is O; or

X is CR 5 R 6 and Y is S, SO, or SO 2 ; or

X is O and Y is CR 8 R 9 ;

wherein when the ---- bond between X and Y is a double bond, then:

X is CR 5 and Y is CR 8 ; and

wherein when the ---- bond between X and Y is a triple bond, then:

X is C and Y is C;

Ring Z is C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl;

R N is H, C 1-4 alkyl, or CN;

R 1 is halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, or C 1-4 haloalkoxy;

R 2 is selected from H, halo, CN, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 hydroxyalkyl, C 1-4 cyanoalkyl, C 1-4 alkoxy, C 1-4 alkoxy-C 1-4 alkyl, C 1-4 haloalkoxy, and C 3-7 cycloalkyl;

R 3 is H, C 1-4 alkyl, —C(═O)—(C 1-6 alkyl), or —S(═O) 2 —(C 1-6 alkyl); or

R 3 and R 5 , together with the atoms to which they are attached and together with any intervening atoms, form a C 5-7 membered cycloalkyl ring or a 5-7 membered heterocycloalkyl ring, each optionally substituted by 1, 2, or 3 substituents independently selected from oxo, halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, and C 1-4 haloalkoxy; or

R 3 and R 8 , together with the atoms to which they are attached and together with any intervening atoms, form a C 5-7 membered cycloalkyl ring or a 5-7 membered heterocycloalkyl ring, each optionally substituted by 1, 2, or 3 substituents independently selected from oxo, halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, and C 1-4 haloalkoxy;

each R 4 is independently F, Cl, nitro, cyano, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 alkoxy, or C 1-4 haloalkoxy;

or two adjacent R 4 together with the atoms to which they are attached form a fused phenyl ring, C 3-7 cycloalkyl ring, 5-7 membered heteroaryl ring, or 4-7 membered heterocycloalkyl ring, each optionally substituted with 1, 2, or 3 substituents independently selected from oxo, halo, nitro, cyano, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 alkoxy, and C 1-4 haloalkoxy; or

R 4 and R 9 , together with the atoms to which they are attached and together with any intervening atoms, form a C 5-7 membered cycloalkyl ring fused with ring Z or a 5-7 membered heterocycloalkyl ring fused with ring Z, each optionally substituted by 1, 2, or 3 substituents independently selected from oxo, halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, and C 1-4 haloalkoxy;

R 5 , R 6 , R 8 , and R 9 are each independently selected from H, halo, NH 2 , OH, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, C 1-4 alkoxy, and C 1-4 haloalkoxy;

m is 0, 1, or 2; and

n is 0, 1, 2, 3, 4, or 5.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is N and W is O.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein ---- is a single bond, X is CR 5 R 6 , and Y is O.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring Z is phenyl.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring Z is 5-6 membered heteroaryl.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring Z is selected from the following (a)-(k):

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is halo, C 1-4 alkyl, or C 1-4 alkoxy.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from H, halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, and C 3-7 cycloalkyl.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is H, C 1-4 alkyl, —C(═O)—(C 1-6 alkyl), or —S(═O) 2 —(C 1-6 alkyl).

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently F, Cl, nitro, cyano, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 alkoxy, or C 1-4 haloalkoxy.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 and R 6 are each independently selected from H, F, NH 2 , and OH.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 8 and R 9 are each independently selected from H and methyl.

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 0.

14. The compound of claim 1 selected from:

2-(4-Chlorophenoxy)-N-(4-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)acetamide-;

2-((4-Chlorophenyl)thio)-N-(4-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)acetamide;

(E)-3-(4-chlorophenyl)-2,3-difluoro-N-(4-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)acrylamide;

3-(4-Chlorophenyl)-N-(4-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)propiolamide;

3-(4-Cyano-3,5-difluorophenyl)-N-(3-(pyridin-4-yl)-1H-pyrazol-5-yl)propanamide;

3-(4-Chlorophenyl)-N-(3-(3-methylpyridin-4-yl)-1H-pyrazol-5-yl)propanamide;

2-((4-chlorophenyl)sulfinyl)-N-(4-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)acetamide;

2-((4-chlorophenyl)sulfonyl)-N-(4-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)acetamide; and

4-Chlorobenzyl (4-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)carbamate;

or a pharmaceutically acceptable salt of any of the aforementioned.

15. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

16. A method of treating or preventing a neurological disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignments (1)

Continuity (2)

References Cited (124)