Compositions, synthesis, and methods of utilizing quinazolinedione derivatives

• US 8,575,185 B2
• Filed: 02/26/2010
• Issued: 11/05/2013
• 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, Dadiboyena, Sureshbabu, Adiey, Kouacou
• Primary Examiner(s): MCDOWELL, BRIAN E
• Application Number:
  US12/714,407
• Publication Number:
  US 20100222359A1
• Time in Patent Office: 1,348 Days
• Field of Search: 544/285
• US Class Current: 514/266.3
• 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 quinazolinedione derivatives of Formulae Ia and Ib, which can be advantageously used for treating schizophrenia and related psychoses such as acute manic, bipolar disorder, autistic disorder, depression and dementia.

Claims

1. A compound according to Formula (1):

2. The compound of claim 1 having Formula 1a:

3. The compound of claim 1 having Formula 1b:

4. The compound of claim 1, 2 or 3 wherein A is —

O—

(CH₂)_n.

5. The compound of claim 3 wherein R³ and R⁴ are hydrogen.

6. The compound of claim 1, 2 or 3 wherein one or both of R¹ and R² are independently halogen-or alkoxy.

7. A pharmaceutical composition comprising the compound of any one of claims 1-3 and a pharmaceutically acceptable carrier.

8. The compound according to claim 3, wherein said compound is

9. The compound according to claim 8, wherein said compound is

10. The compound according to claim 8, wherein the pharmaceutically acceptable salt is a hydrochloride.

11. The compound according to claim 8, wherein R¹ is H and R² is methoxy.

18. The compound of claim 5, wherein R⁵ and R⁶ are hydrogen.

19. The compound of claim 18, wherein one or both of R¹ and R² are independently halogen-or alkoxy.

20. A method of treating one of psychoses, schizophrenia, acute mania, bipolar disorder, or depression comprising administering to a patient in need thereof the compound of any one of claims 1-3 and 8-10.

21. A method of treating schizophrenia comprising administering to a patient in need thereof the compound of any one of claims 1-3 and 8-10.

22. A method of treating bipolar disorder comprising administering to a patient in need thereof the compound of any one of claims 1-3 and 8-10.

12. A compound according to Formula (1b):

13. A pharmaceutical composition comprising the compound of claim 12 and a pharmaceutically acceptable carrier.

14. The compound of claim 12, wherein A is —

(CH₂)_n—

.

15. The compound of claim 14, wherein R³ and R⁴ are hydrogen.

16. The compound of claim 15, wherein R⁵ and R⁶ are hydrogen.

17. The compound of claim 16, wherein one or both of R¹ and R² are independently halogen-or alkoxy.

23. A method of treating one of psychoses, schizophrenia, acute mania, bipolar disorder, or depression comprising administering to a patient in need thereof the compound of claim 12.

24. A method of treating schizophrenia comprising administering to a patient in need thereof the compound of claim 12.

25. A method of treating bipolar disorder comprising administering to a patient in need thereof the compound of claim 12.