Substituted heterocyclic compounds

Patent metadata

Field	Value
Publication number	US-11866414-B2
Application number	US-202217743557-A
Country	US
Kind code	B2
Filing date	May 13, 2022
Priority date	May 14, 2021
Publication date	Jan 9, 2024
Grant date	Jan 9, 2024

Abstract

There are disclosed compounds of the following formula I:

or a stereoisomer or pharmaceutically acceptable salt thereof, wherein all substituents are as defined herein, which are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition. The compounds of the invention may be useful for treating neurodegenerative diseases or disorders.

First claim

We claim:

1. A compound having the structure

or a pharmaceutically-acceptable salt thereof.

2. The compound according to claim 1 which is

or a pharmaceutically-acceptable salt thereof.

3. The compound according to claim 1 which is

or a pharmaceutically-acceptable salt thereof.

4. The compound according to claim 2 which is

or a pharmaceutically-acceptable salt thereof.

5. The compound according to claim 2 which is

or a pharmaceutically-acceptable salt thereof.

6. The compound according to claim 3 which is

or a pharmaceutically-acceptable salt thereof.

7. The compound according to claim 4 having the structure

8. The compound according to claim 4 having the structure

9. The compound according to claim 4 having the structure

10. The compound according to claim 5 having the structure

11. The compound according to claim 5 having the structure

12. The compound according to claim 5 having the structure

13. The compound according to claim 6 having the structure

14. The compound according to claim 6 having the structure

15. The compound according to claim 6 having the structure

16. The compound according to claim 1 having the structure

17. A compound having the structure

18. A pharmaceutically acceptable salt of a compound having the structure

19. A compound having the structure

20. A compound or a pharmaceutically acceptable salt thereof selected from
6-cyclopropaneamido-4-{[4-(2-cyclopropyl-2H-1,2,3-triazol-4-yl)-3-methoxypyridin-2-yl]amino}-N—( 2 H3)methylpyridazine-3-carboxamide,
6-(cyclopropanecarboxamido)-4-((3-methoxy-4-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-N-(methyl-d3)pyridazine-3-carboxamide,
6-((1S,2S)-2-fluorocyclopropane-1-carboxamido)-4-((3-methoxy-4-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-N-(methyl-d 3 )pyridazine-3-carboxamide,
6-(2,2-dimethylcyclopropane-1-carboxamido)-4-((3-methoxy-4-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-N-(methyl-d 3 )pyridazine-3-carboxamide,
6-(3,3-dimethylureido)-4-((3-methoxy-4-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-N-(methyl-d 3 )pyridazine-3-carboxamide,
4-((3-methoxy-4-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-N-(methyl-d 3 )-6-((1S,2R)-2-methylcyclopropane-1-carboxamido)pyridazine-3-carboxamide,
6-(cyclopropanecarboxamido)-4-((3-methoxy-6-methyl-4-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-N-(methyl-d 3 )pyridazine-3-carboxamide,
(E)-(6-((cyclopropanecarbonyl)imino)-4-((3-methoxy-4-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-3-((methyl-d3)carbamoyl)pyridazin-1(6H)-yl)methyl dihydrogen phosphate,
6-(cyclopropane-carboxamido)-4-((3-methoxy-4-(2-(methyl-d 3 )-2H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-N-(methyl-d 3 )pyridazine-3-carboxamide, or
6-(Cyclopropanecarboxamido)-4-((6-fluoro-3-methoxy-4-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-N-(methyl-d 3 )pyridazine-3-carboxamide.

21. A pharmaceutical composition comprising one or more compounds according to claim 1 and a pharmaceutically acceptable carrier or diluent.

22. A method of treating a disease, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound according to claim 1 , wherein the disease is a neurodegenerative disease.

23. A method of treating a disease, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound according to claim 22 , wherein the disease is a neurodegenerative disease selected from Alzheimer's disease, Parkinson's disease, ALS or multiple sclerosis.

Assignees

• Bristol Myers Squibb Co

Inventors

• Spergel Steven H
• Moslin Ryan M
• Mertzman Michael Edward
• Xiao Zili

Classifications

• C07D249/04 Primary

  1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles · CPC title

• A61K31/501 Primary

  not condensed and containing further heterocyclic rings · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title