Compounds having unique CB1 receptor binding selectivity and methods for their production and use

• US 6,825,209 B2
• Filed: 04/15/2002
• Issued: 11/30/2004
• Est. Priority Date: 04/15/2002
• Status: Expired due to Fees

• Current Assignee: Research Triangle Institute
• Original Assignee: Research Triangle Institute
• Inventors: Seltzman, Herbert H., Thomas, Brian F., Francisco, Maria Elena Y.
• Primary Examiner(s): AULAKH, CHARANJIT
• Application Number:
  US10/121,708
• Publication Number:
  US 20030199536A1
• Time in Patent Office: 960 Days
• Field of Search: 514/285, 514/403, 514/406, 514/909, 546/70, 548/374.1
• US Class Current: 514/285
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: C07D 231/14 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Compounds are provided that are amide analogs of SR141716A having unique CB1 receptor selectivity and providing WIN sparing binding characteristics, pharmaceutical compositions containing the compounds and their use in a method of treatment of CB1 receptor related disorders, such as obesity, schizophrenia, memory dysfunction and marijuana abuse.

Claims

1. A compound of formula (III)

wherein R is a linear or branched hydrocarbon group having from 7 to 12 carbons, or N-piperidinyl.

2. The compound of claim 1, wherein R is a linear alkyl group.

3. The compound of claim 1, wherein R is a member selected from the group consisting of heptyl, octyl and nonyl.

4. A pharmaceutical composition, comprising:

an alkyl amide of formula (III)

wherein R is a linear or branched hydrocarbon group having from 7 to 12 carbons, or N-piperidinyl, and a pharmaceutically acceptable carrier.

5. The pharmaceutical composition of claim 4, wherein R is a linear alkyl group.

6. The pharmaceutical composition of claim 4, wherein R is a member selected from the group consisting of heptyl, octyl and nonyl.

7. A method for the treatment of obesity, comprising:

administering to a subject in need thereof, an effective amount of an alkyl amide compound of Formula (III)

wherein R is a linear or branched hydrocarbon group having from 7 to 12 carbons, or N-piperidinyl.

8. The method of claim 7, wherein R is a linear alkyl group.

9. The method of claim 7, wherein R is a member selected from the group consisting of heptyl, octyl and nonyl.

10. The method of claim 7, wherein said effective amount is an amount of from 0.01 mg/kg to 900 mg/kg.

11. The method of claim 7, wherein said administering is performed by a method of administration selected from the group consisting of oral, intravenous, peritoneal, and nasal administration routes.

12. A compound:

of formula (II)

wherein R is a linear or branched hydrocarbon group having from 9 to 12 carbons.

13. The compound of claim 12, wherein R is a linear alkyl group.

14. The compound of claim 12, wherein R is nonyl.

15. A pharmaceutical composition, comprising:

an alkyl amide of formula (II)

wherein R is a linear or branched hydrocarbon group having from 9 to 12 carbons, and a pharmaceutically acceptable carrier.

16. The pharmaceutical composition of claim 15, wherein R is a linear alkyl group.

17. The pharmaceutical composition of claim 15, wherein R is nonyl.

18. A method for the treatment of obesity, comprising:

administering to a subject in need thereof, an effective amount of an alkyl amide compound of Formula (II) having WIN-sparing properties

wherein R is a linear or branched hydrocarbon group having from 9 to 12 carbons.

19. The method of claim 18, wherein R is a linear alkyl group.

20. The method of claim 18, wherein R is nonyl.

21. The method of claim 18, wherein said effective amount is an amount of from 0.01 mg/kg to 900 mg/kg.

22. The method of claim 18, wherein said administering is performed by a method of administration selected from the group consisting of oral, intravenous, peritoneal, and nasal administration routes.