Arylpiperazine derivatives and methods of utilizing same

• US 8,980,883 B2
• Filed: 09/17/2014
• Issued: 03/17/2015
• 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:
  US14/489,331
• Publication Number:
  US 20150005298A1
• Time in Patent Office: 181 Days
• Field of Search: 514/224.2, 544/52
• US Class Current: 514/224.2
• 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 which can be advantageously used for treating schizophrenia and related psychoses such as acute manic, bipolar disorder, autistic disorder, and depression.

Claims

1. A compound of Formula 1:

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

3. The compound of claim 2, 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 compound of claim 2, 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 compound of claim 2, wherein A is —

(CH₂)_n—

.

6. The compound of claim 2, wherein R⁴ is H.

7. The compound of claim 2, wherein R¹ and R² are independently H, halogen, or alkoxy.

8. The compound of claim 7, wherein R¹ is H, and R² is methoxy.

9. The compound of claim 2, wherein R¹ and R² are chloro.

10. The compound of claim 7, wherein A is —

O—

(CH₂)_n—

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

11. The compound of claim 7, wherein R³, R⁴, R⁶, R⁷ and R⁸ are hydrogen.

12. The compound of claim 2, wherein R¹, R², R³, R⁴, R⁶, R⁷ and R⁸ and A are optionally substituted with ²H (deuterium).

13. The compound of claim 1, wherein the compound is in the form of a hydrochloride salt.

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

15. A pharmaceutical composition comprising the compound of claim 1, and a pharmaceutically acceptable carrier, excipient, or diluent.

16. A method of treating psychosis, schizophrenia, acute mania, bipolar disorder, autistic disorder or depression, the method comprising administering to a patient in need thereof the pharmaceutical formulation claim 15.

17. The method of claim 16, wherein said method treats depression.

18. The method of claim 16, wherein said method treats schizophrenia.

19. The method of claim 16, wherein said method treats psychosis.

20. The method of claim 16, wherein said method treats autistic disorder.