PDE10 inhibitors and related compositions and methods

Patent metadata

Field	Value
Publication number	US-9783521-B2
Application number	US-201313742199-A
Country	US
Kind code	B2
Filing date	Jan 15, 2013
Priority date	Aug 5, 2008
Publication date	Oct 10, 2017
Grant date	Oct 10, 2017

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 method for treating neurological disorders in a warm-blooded animal in need thereof, comprising administering to the animal an effective amount of a compound having the following structure (I):

or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof,
wherein:
X is —O— or —S—;
R 1 is C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 aralkyl, aryl, —(CH 2 ) n O(CH 2 ) m CH 3 or —(CH 2 ) n N(CH 3 ) 2 ;
R 2 and R 3 are the same or different and independently substituted or unsubstituted heterocyclyl, or substituted or unsubstituted aryl; and
R 4 and R 5 are the same or different and independently hydrogen, C 1-6 alkyl or C 1-6 haloalkyl;
n is 1,2, 3,4, 5 or 6; and
m is 0, 1, 2, 3, 4, 5 or 6,

wherein the neurological disorder is Parkinson's disease, Huntington's disease, schizophrenia, or obsessive-compulsive disorder.

2. The method of claim 1 wherein the neurological disorder is schizophrenia.

3. The method of claim 1 wherein the neurological disorder is Huntington's disease.

4. The method of claim 1 wherein the compound has the following structure (II):

5. The method of claim 4 wherein R 4 and R 5 are the same or different and independently hydrogen or C 1-6 alkyl.

6. The method of claim 4 wherein R 4 and R 5 are hydrogen.

7. The method of claim 4 wherein R 1 is C 1-6 alkyl.

8. The method of claim 7 wherein R 1 is methyl.

9. The method of claim 7 wherein R 1 is ethyl.

10. The method of claim 7 wherein R 1 is isopropyl.

11. The method of claim 4 wherein R 3 is substituted phenyl.

12. The method of claim 11 wherein R 3 is 3,4,5-trimethoxyphenyl.

13. The method of claim 11 wherein R 3 is 4-bromo-3,5-dimethoxyphenyl.

14. The method of claim 4 wherein R 2 is substituted or unsubstituted phenyl.

15. The method of claim 14 wherein R 2 is 4-morpholinophenyl.

16. The method of claim 14 wherein R 2 is 4-(1H-pyrazol-1-yl)phenyl.

17. The method of claim 4 wherein R 2 is substituted or unsubstituted naphthyl.

18. The method of claim 4 wherein R 2 is substituted or unsubstituted heteroaryl.

19. The method of claim 1 wherein the compound has the following structure (III):

20. The method of claim 19 wherein R 4 and R 5 are the same or different and independently hydrogen or C 1-6 alkyl.

21. The method of claim 19 wherein R 4 and R 5 are hydrogen.

22. The method of claim 19 wherein R 1 is C 1-6 alkyl.

23. The method of claim 22 wherein R 1 is methyl.

24. The method of claim 22 wherein R 1 is ethyl.

25. The method of claim 22 wherein R 1 is isopropyl.

26. The method of claim 19 wherein R 3 is substituted phenyl.

27. The method of claim 26 wherein R 3 is 3,4,5-trimethoxyphenyl.

28. The method of claim 26 wherein R 3 is 4-bromo-3,5-dimethoxyphenyl.

29. The method of claim 19 wherein R 2 is substituted or unsubstituted phenyl.

30. The method of claim 29 wherein R 2 is 4-morpholinophenyl.

31. The method of claim 29 wherein R 2 is 4-(1H-pyrazol-1-yl)phenyl.

32. The method of claim 19 wherein R 2 is substituted or unsubstituted naphthyl.

33. The method of claim 19 wherein R 2 is substituted or unsubstituted heteroaryl.

Assignees

• Omeros Corp

Inventors

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

Classifications

• A61P43/00

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/22

  Anxiolytics · CPC title

• C07D235/16

  Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07C251/88

  having also the other nitrogen atom doubly-bound to a carbon atom, e.g. azines · CPC title