Substituted heterocyclic compounds

Patent metadata

Field	Value
Publication number	US-2024270723-A1
Application number	US-202218560496-A
Country	US
Kind code	A1
Filing date	May 13, 2022
Priority date	May 14, 2021
Publication date	Aug 15, 2024
Grant date	—

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 of formula I

or a stereoisomer or pharmaceutically acceptable salt thereof,

wherein
X, X 1 and X 2 are —N— or —CH—, with the proviso that if X is —CH—, one of X 1 and X 2 must be —N—, and
if X is —N—, one of X 1 and X 2 must be —N—;
Y is —CH— or —N—;
R 1 is OR 1a , NR 1a R 1b or R 2 ;
R 1a and R 1b are independently hydrogen or C 1-3 alkyl;
R 2 is C 3-6 cycloalkyl substituted with 0-2 R 2a ;
R 2a is F or C 1-3 alkyl;
R 3 is C 1-3 alkyl or C 3-6 cycloalkyl; and
R 4 is hydrogen, halogen or C 1-3 alkyl.

2 . The compound according to claim 1 of formula II

or a stereoisomer or pharmaceutically acceptable salt thereof,

wherein
X, X 1 and X 2 are —N— or —CH—, with the proviso that if X is —CH—, one of X 1 and X 2 must be —N—, and
if X is —N—, one of X 1 and X 2 must be —N—;
Y is —CH— or —N—;
R 3 is C 1-3 alkyl or C 3-6 cycloalkyl.

3 . The compound according to claim 1 of formula III

or a stereoisomer or pharmaceutically acceptable salt thereof,
X, X 1 and X 2 are —N— or —CH—, with the proviso that if X is —CH—, one of X 1 and X 2 must be —N—, and
if X is —N—, one of X 1 and X 2 must be —N—;
R 3 is C 1-3 alkyl or C 3-6 cycloalkyl.

4 . A compound or a pharmaceutically acceptable salt thereof, selected from
6-cyclopropaneamido-4-{[5-methoxy-6-(2-methyl-2H-1,2,3-triazol-4-yl)pyrimidin-4-yl]amino}-N-( 2 H3)methylpyridazine-3-carboxamide, 6-cyclopropaneamido-4-{[3-methoxy-2-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-4-yl]amino}-N-( 2 H3)methylpyridazine-3-carboxamide, 4-{[3-methoxy-2-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-4-yl]amino}-N-( 2 H3)methyl-6-[(1R)-spiro[2.2]pentane-1-amido]pyridazine-3-carboxamide, 6-cyclopropaneamido-4-{[2-(1-cyclopropyl-1H-pyrazol-4-yl)-3-methoxypyridin-4-yl]amino}-N-( 2 H3)methylpyridazine-3-carboxamide, and 6-cyclopropaneamido-4-{[2-(2-cyclopropyl-2H-1,2,3-triazol-4-yl)-3-methoxypyridin-4-yl]amino}-N-( 2 H3)methylpyridazine-3-carboxamide.

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

6 . A pharmaceutical composition comprising one or more compounds according to claim 4 and a pharmaceutically acceptable carrier or diluent.

7 . 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.

8 . The method of claim 7 wherein the neurodegenerative disease is Alzheimer's disease, Parkinson's disease, ALS, Multiple Sclerosis (RMS and/or progressive MS, including CIS, optic neuritis, neuromyelitis optica).

Assignees

• Bristol Myers Squibb Co

Inventors

• Spergel Steven H
• Mertzman Michael Edward

Classifications

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61K31/501

  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