PDE10 inhibitors and related compositions and methods

Patent metadata

Field	Value
Publication number	US-10106516-B2
Application number	US-201615229020-A
Country	US
Kind code	B2
Filing date	Aug 4, 2016
Priority date	Mar 12, 2010
Publication date	Oct 23, 2018
Grant date	Oct 23, 2018

Abstract

Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing a compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.

First claim

What is claimed is:

1. A compound having the following structure (I-E):

or a pharmaceutically acceptable salt, stereoisomer, solvate, or isotope thereof,
wherein:
R 1 is C 1-6 alkyl;
R 2 is phenyl substituted with morpholino, pyrazolyl, triazolyl, pyridinyl, or pyrazinyl; and
R 3 is aryl substituted with at least one halogen, alkyl, hydroxy, alkoxy, or cyano.

2. The compound of claim 1 , wherein R 1 is methyl, ethyl, or propyl.

3. The compound of claim 1 , wherein R 3 is phenyl substituted with at least one halogen, alkyl, hydroxy, alkoxy, or cyano.

4. The compound of claim 3 , wherein R 3 is phenyl substituted with at least one halogen and at least one alkoxy.

5. The compound of claim 3 , wherein R 3 is 4-bromo-3,5-dimethoxyphenyl, 4-chloro-3,5-dimethoxyphenyl, 4-fluoro-3,5-dimethoxyphenyl, 3-bromo-4,5-dimethoxyphenyl, 3-chloro-4,5-dimethoxyphenyl, 3-fluoro-4,5-dimethoxyphenyl, 4-cyano-3,5-dimethoxyphenyl, 3-cyano-4,5-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 4-hydroxy-3,5-dimethoxyphenyl, or 4-methyl-3,5-dimethoxyphenyl.

6. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt, stereoisomer, solvate, or isotope thereof.

7. The compound of claim 1 , wherein the compound is an isotope having one or more atoms replaced by the same atom having a different atomic mass.

8. The isotope of claim 7 , wherein one or more H atoms is replaced by 2 H.

9. The isotope of claim 7 , wherein one or more H atoms is replaced by 3 H.

10. The isotope of claim 7 , wherein one or more C atoms is replaced by 14 C.

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

12. A compound having the following structure:

or a pharmaceutically acceptable salt, stereoisomer, solvate, or isotope thereof.

Assignees

• Omeros Corp

Inventors

• Cutshall Neil S
• Gage Jennifer Lynn
• Wheeler Thomas Neil
• Little Thomas L

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• A61P25/22

  Anxiolytics · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title