Gsk-3 inhibitors

Patent metadata

Field	Value
Publication number	US-2019276463-A1
Application number	US-201716463451-A
Country	US
Kind code	A1
Filing date	Nov 27, 2017
Priority date	Nov 28, 2016
Publication date	Sep 12, 2019
Grant date	—

Abstract

The disclosure generally relates to compounds of formula (I), including their salts, as well as compositions and methods of using the compounds to treat disorders associated with GSK-3.

First claim

We claim:

1 . A compound of formula I

where:
R 1 is hydrogen or N(R 3 )(R 4 );
R 2 is hydrogen, alkyl, cycloalkyl, or cycloalkenyl;
or R 2 is pyridinyl or phenyl and is substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy;
R 3 is hydrogen, alkyl, (cycloalkyl)alkyl, cycloalkyl, alkylcarbonyl, or cycloalkylcarbonyl;
R 4 is hydrogen;
Ar 1 is 3-pyridinyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyrimidinyl, or 2-pyrazinyl, and is substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylsulfonyl, N(R 3 )(R 4 ), or Ar 2 ; and
Ar 2 is phenyl substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, haloalkoxy;
or a pharmaceutically acceptable salt thereof.

2 . A compound of claim 1 where R 1 is N(R 3 )(R 4 ) and R 2 is hydrogen.

3 . A compound of claim 1 where R 1 is hydrogen and R 2 is not hydrogen.

4 . A compound of claim 1 where Ar 1 is 3-pyridinyl substituted with 0-3 substituents selected from the group consisting of cyano, halo, alkyl, haloalkyl, (R 2 )alkyl, alkoxy, haloalkoxy, and R 2 .

5 . A compound of claim 1 where Ar 1 is 5-pyrimidinyl substituted with 0-3 substituents selected from the group consisting of cyano, halo, alkyl, haloalkyl, (R 2 )alkyl, alkoxy, haloalkoxy, and R 2 .

6 . A compound of claim 1 where Ar 2 is phenyl substituted with 0-3 substituents selected from the group consisting of cyano, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylsulfinyl, and alkylsulfonyl.

7 . A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

8 . A method for the treatment of a disease, disorder, or condition selected from the group consisting of neurodegenerative disorders, psychiatric disorders, cancer, metabolic disorders, and inflammatory disorders which comprises administering to a patient a therapeutically affective amount of a compound of claim 1 .

9 . A method for the treatment of a condition selected from the group consisting of Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy, argyophilic grain disease, corticobasal degeneration, Pick's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, Huntington's disease, peripheral neuropathy, traumatic brain injury, spinal cord trauma, and vascular dementia, which comprises administering to a patient a therapeutically affective amount of a compound of claim 1 .

10 . The method of claim 9 directed to the treatment of Alzheimer's disease.

Assignees

• Bristol Myers Squibb Co

Inventors

• Hartz Richard A
• Ahuja Vijay T
• Sivaprakasam Prasanna
• Dubowchik Gene M
• Macor John E

Classifications

• A61K31/5025

  ortho- or peri-condensed with heterocyclic ring systems · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · 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