Granted Patent B2

US 8,343,970 · App. 13/045,162 · Granted Jan 1, 2013

Abstract

Claims (62)

1. A compound of the following structure (I):

or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof,

wherein:

A is:

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 is (i) substituted or unsubstituted aryl or (ii) substituted or unsubstituted heterocyclyl;

R 3 is substituted or unsubstituted aryl;

R 4 is 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.

2. A compound of claim 1 the following structure (I-A):

3. A compound of claim 1 of the following structure (I-B):

4. A compound of claim 1 of the following structure (I-C):

5. A compound of claim 1 of the following structure (I-D):

6. A compound of claim 1 of the following structure (I-E):

7. A compound of claim 1 of the following structure (I-F):

8. A compound of claim 1 of the following structure (I-G):

9. A compound of claim 1 of the following structure (I-H):

10. A compound of claim 1 of the following structure (I-I):

11. The compound of claim 1 wherein R 4 is hydrogen.

12. The compound of claim 1 wherein R 4 is C 1-6 alkyl.

13. The compound of claim 12 wherein R 4 is methyl.

14. The compound of claim 1 wherein R 1 is C 1-6 alkyl.

15. The compound of claim 14 wherein R 1 is methyl.

16. The compound of claim 14 wherein R 1 is ethyl.

17. The compound of claim 1 wherein R 3 is substituted or unsubstituted phenyl.

18. The compound of claim 17 wherein R 3 is substituted phenyl.

19. The compound of claim 18 wherein R 3 is 4-bromo-3,5-dimethoxyphenyl.

20. The compound of claim 18 wherein R 3 is 4-chloro-3,5-dimethoxyphenyl.

21. The compound of claim 18 wherein R 3 is 3,4,5-trimethoxyphenyl.

22. The compound of claim 1 wherein R 2 is substituted or unsubstituted aryl.

23. The compound of claim 22 wherein R 2 is substituted or unsubstituted phenyl.

24. The compound of claim 23 wherein R 2 is substituted phenyl.

25. The compound of claim 24 wherein R 2 is phenyl substituted with C 1-6 alkoxy.

26. The compound of claim 24 wherein R 2 is phenyl substituted with substituted or unsubstituted heterocyclyl.

27. The compound of claim 26 wherein R 2 is phenyl substituted with substituted heterocyclyl.

28. The compound of claim 27 wherein R 2 is 4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl.

29. The compound of claim 27 wherein R 2 is 4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl.

30. The compound of claim 26 wherein R 2 is phenyl substituted with unsubstituted heterocyclyl.

31. The compound of claim 30 wherein R 2 is 4-morpholinophenyl.

32. The compound of claim 1 wherein R 2 is substituted or unsubstituted heterocyclyl.

33. The compound of claim 1 wherein the compound is:

1-(5-(4-bromo-3,5-dimethoxyphenyl)furan-2-yl)-2-methoxy-2-(4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl)ethanone;

2-methoxy-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)-1-(5-(3,4,5-trimethoxyphenyl)furan-2-yl)ethanone;

1-(5-(4-bromo-3,5-dimethoxyphenyl)furan-2-yl)-2-ethoxy-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)ethanone;

1-(5-(4-chloro-3,5-dimethoxyphenyl)furan-2-yl)-2-methoxy-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)ethanone;

1-(5-(4-chloro-3,5-dimethoxyphenyl)furan-2-yl)-2-ethoxy-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)ethanone;

1-(5-(4-chloro-3,5-dimethoxyphenyl)furan-2-yl)-2-methoxy-2-(4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl)ethanone; or

1-(5-(4-chloro-3,5-dimethoxyphenyl)furan-2-yl)-2-ethoxy-2-(4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl)ethanone.

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

35. A method for inhibiting PDE10 in a warm-blooded animal, comprising administering to the animal an effective amount of a compound of claim 1 or a pharmaceutical composition of claim 34 .

36. A method for treating a neurological disorder disorders in a warm-blooded animal having said neurological disorder, comprising administering to the animal an effective amount of a compound of claim 1 or a pharmaceutical composition of claim 34 , wherein the neurological disorder is selected from the group consisting of psychotic disorders, anxiety disorders, 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, bipolar disorders, post-traumatic stress disorders, drug-induced psychosis, panic disorders, obsessive-compulsive disorders, attention-deficit disorders, disruptive behavior disorders, autism, depression, dementia, epilepsy, insomnias and multiple sclerosis.

37. The method of claim wherein the neurological disorder is schizophrenia.

38. The method of claim wherein the neurological disorder is post-traumatic stress disorder.

39. The compound of claim 1 wherein the compound is:

1-(5-(4-bromo-3,5-dimethoxyphenyl)furan-2-yl)-2-ethoxy-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)ethanone.

40. The compound of claim 1 wherein the compound is:

1-(5-(4-chloro-3,5-dimethoxyphenyl)furan-2-yl)-2-ethoxy-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)ethanone.

41. The compound of claim 1 wherein the compound is:

1-(5-(4-chloro-3,5-dimethoxyphenyl)furan-2-yl)-2-methoxy-2-(4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl)ethanone.

42. The compound of claim 1 wherein the compound is:

1-(5-(4-chloro-3,5-dimethoxyphenyl)furan-2-yl)-2-ethoxy-2-(4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl)ethanone.

Assignments (6)