1-Phenyl-2(1H,3H)-indolone psychotherapeutic agents

• US 4,879,391 A
• Filed: 08/03/1987
• Issued: 11/07/1989
• Est. Priority Date: 09/20/1982
• Status: Expired due to Term

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Howard, Harry R. Jr., Sarges, Reinhard
• Primary Examiner(s): Sneed, H. M. S.
• Assistant Examiner(s): Pak, Chung K.
• Application Number:
  US07/081,262
• Time in Patent Office: 827 Days
• Field of Search: 548/486, 548/466, 514/418
• US Class Current: 548/486
• CPC Class Codes: C07C 43/225 containing halogen
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 209/34 in position 2
• CPC Class Codes: C07D 209/38 in positions 2 and 3, e.g. isatin

Abstract

Certain substituted 1-phenyl-3-(aminoalkylidene)-2(1H,3H)-indolones are highly potent gabaergic agents, valuable in the treatment of individuals suffering from schizophrenia or reversing the side effects of a previously or concurrently administered neuroleptic agent; or in the treatment of epilepsy. A wider class of substituted 1-phenyl-3-(aminoalkylidene)-2(1H,3H)-indolones, together with 1-phenyl-3-(2-pyrrolidinylidiene-2(1H,3H)-indolones, and homologs thereof, are valuable in the treatment of anxiety.

Claims

1. A compound of the formula ##STR8## wherein:

A is hydrogen or methyl;

R is hydrogen, methyl or ethyl;

X is hydrogen, (C₁ -C₂)alkyl;

(C₁ -C₂)alkkoxy, (C₁ -C₂)alkylthio;

chloro, fluoro or trifluoromethyl;

Y is hydrogen, (C₁ -C₂≢

)alkyl, (C₁ -C₂)alkoxy or (C₁ -C₂)alkylthio; and

Z and Z¹ are each independently hydrogen or methyl;

with the provisos that;

at least one of X, Y, Z and Z¹ is other than hydrogen;

at least one of X and Y is other than (C₁ -C₂)alkoxy; and

when R is methyl, A is also methyl.

2. A compound of claim 1 wherein Z¹ and Z are hydrogen.

3. A compound of claim 2 wherein X is chloro and Y is hydrogen.

4. The compound of claim 3 wherein both A and R are hydrogen.

5. The compound of claim 3 wherein A is hydrogen and R is ethyl.

6. The compound of claim 3 wherein both A and R are methyl.

7. A compound of claim 2 wherein both A and R are methyl and Y is hydrogen.

8. The compound of claim 7 wherein X is methyl.

9. A compound of claim 2 wherein R is methyl and Y is methoxy.

10. The compound of claim 9 wherein A is methyl and X is chloro.

11. A pharmaceutical composition suitable for the treatment of a person suffering from schizophrenia which comprises a pharmaceutically-acceptable carrier and a compound of claim 1 in an amount which will alleviate said schizophrenia.

12. A method of treating a person suffering from schizophrenia which comprises administration to said person a compound of the formula ##STR9## wherein:

A is hydrogen or methyl;

R is hydrogen or (C₁ -C₂)allkyl;

X is hydrogen, (C₁ -C₂)alkyl;

(C₁ -C₂)alkoxy, (C₁ -C₂)alkylthio;

chloro, fluoro or trifluoromethyl;

Y is hydrogen, (C₁ -C₂)alkyl, (C₁ -C₂)alkoxy or (C₁ -C₂)alkythio; and

Z and Z¹ are each independently hydrogen or methyl;

with the provisos that;

at least one of X, Y, Z and Z¹ is other than hydrogen; and

at least one of X and Y is other than (C₁ -C₂)alkoxy;

in an amount sufficient to alleviate said schizophrenia.

13. A method of claim 12 wherein Z¹ and Z are hydrogen.

14. A method of claim 13 wherein X is chloro and Y is hydrogen.

15. The method of claim 14 wherein both A and R are hydrogen.

16. The method of claim 14 wherein A is hydrogen and R is methyl.

17. The method of claim 14 wherein A is hydrogen and R is ethyl.

18. The method of claim 14 wherein both A and R are methyl.

19. A method of claim 13 wherein both A and Y are hydrogen and R is methyl.

20. The methods of claim 19 wherein X is (C₁ -C₂)alkyl.

21. The method of claim 19 wherein X is trifluoromethyl.

22. The method of claim 19 wherein X is methoxy.

23. The method of claim 19 wherein X is fluoro.

24. A method of claim 13 wherein both A and R are methyl and Y is hydrogen.

25. The method of claim 24 wherein X is methyl.

26. A method of claim 13 wherein R is methyl and Y is methoxy.

27. The method of claim 26 wherein A is methyl and X is chloro.

28. The method of claim 26 wherein A is hydrogen and X is chloro.

29. The method of claim 26 wherein A is hydrogen and X is fluoro.

30. The method of claim 12 wherein both A and Z¹ are hydrogen, both R and Z are methyl, X is chloro and Y is methoxy.

31. The method of claim 12 wherein A, X, Y and Z are hydrogen, and R and Z¹ are methyl.