Methods of utilizing arylpiperazine derivatives

• US 8,431,570 B2
• Filed: 05/07/2012
• Issued: 04/30/2013
• Est. Priority Date: 02/26/2009
• Status: Active Grant

• Current Assignee: Reviva Pharmaceuticals, Inc.
• Original Assignee: Reviva Pharmaceuticals, Inc.
• Inventors: Bhat, Laxminarayan, Mohapatra, Prabhu Prasad, Adiey, Kouacou
• Primary Examiner(s): HABTE, KAHSAY
• Application Number:
  US13/465,439
• Publication Number:
  US 20120220579A1
• Time in Patent Office: 358 Days
• Field of Search: 544/105, 514/230.5
• US Class Current: 514/230.5
• CPC Class Codes: A61K 31/538 ortho- or peri-condensed with carbocyclic ring systems
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: C07D 265/36 condensed with one six-membered ring
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention provides arylpiperazine derivatives having Formula I which can be advantageously used for treating schizophrenia and related psychoses such as acute manic, bipolar disorder, autistic disorder and depression.

Claims

1. A method of treating psychoses, schizophrenia, acute mania, bipolar disorder, autistic disorder or depression, the method comprising administering to a patient in need thereof a compound of Formula 1:

2. The method according to claim 1, wherein the compound of claim 1 has Formula 1a:

3. The method according to claim 1, wherein A is —

O—

(CH₂)_n—

, —

S—

(CH₂)_n—

, —

CH₂—

O—

(CH₂)_n—

, —

(CH₂)_n—

O—

CH₂—

CH₂—

, —

CH₂—

S—

(CH₂)_n—

, or —

(CH₂)_n—

S—

CH₂—

CH₂—

.

4. The method according to claim 1, wherein A is —

NH—

C(O)—

(CH₂)_n—

, —

CH₂—

NH—

C(O)—

(CH₂)_n—

, —

CH₂—

C(O)—

NH—

(CH₂)_n—

or —

(CH₂)_n—

C(O)—

NH—

CH₂—

CH₂—

.

5. The method according to claim 1, wherein R⁴ is H.

6. The method according to claim 1, wherein R¹ and R² are independently H, halogen, or alkoxy.

7. The method according to claim 6, wherein R¹ is H, and R² is methoxy.

8. The method according to claim 1, wherein R¹ and R² are chloro.

9. The method according to claim 1, wherein A is —

O—

(CH₂)_n—

; and

R³, R⁴, R⁶, R⁷, and R⁸ are independently hydrogen or alkyl.

10. The method according to claim 1, wherein R³, R⁴, R⁶, R⁷, and R⁸ are hydrogen.

11. The method according to claim 1, wherein the hydrogens of R¹, R², R³, R⁴, R⁶, R⁷ and R⁸ and A are optionally substituted with ²H (deuterium).

12. The method according to claim 1, wherein the compound is in the form of a hydrochloride salt.

13. The method according to claim 1, wherein the compound is administered in a pharmaceutical composition comprising a pharmaceutically acceptable carrier, excipient, or diluent.

14. The method according to claim 1, wherein the compound is enantiomerically and/or diastereomerically pure.

15. The method according to claim 1, wherein said method treats psychosis.

16. The method according to claim 1, wherein said method treats schizophrenia.

17. The method according to claim 1, wherein said method treats autistic disorder.

18. The method according to claim 1, wherein said method treats bipolar disorder.

19. The method according to claim 1, wherein said method treats depression.

20. The method of claim 1, wherein n is 4.