Triazolopyridine cannabinoid receptor 1 antagonists

• US 20070004772A1
• Filed: 06/16/2006
• Published: 01/04/2007
• Est. Priority Date: 06/17/2005
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Sun, Chongqing, Wu, Gang, Huang, Yanting, Murugesan, Natesan, Lee, Taekyu, Ewing, William, Sher, Philip, Sulsky, Richard
• Granted Patent: US 7,572,808 B2
• Time in Patent Office: Days
• US Class Current: 514/303
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The present application describes compounds according to Formula I, pharmaceutical compositions comprising at least one compound according to Formula I and optionally one or more additional therapeutic agents, and methods of treatment using the compounds according to Formula I both alone and in combination with one or more additional therapeutic agents. The compounds have the following general formula:
including all prodrugs, solvates, pharmaceutically acceptable salts and stereoisomers, wherein R¹, R², R³, R⁴ and R⁵ are described herein.

Claims

1. A compound or a prodrug or a solvate or a pharmaceutically acceptable salt or a stereoisomer thereof according to Formula I

2. The compound according to claim 1, wherein R¹ is selected from the group consisting of aryl and heteroaryl, either of which may be optionally substituted with 1 to 3 R¹⁰.

3. The compound according to claim 1, wherein R² is aryl which may be optionally substituted with 1 to 3 R¹⁰.

4. The compound according to claim 1, wherein R³ is selected from the group consisting of aryl and heteroaryl, either of which may be optionally substituted with 1 to 3 R¹⁰.

5. The compound according to claim 1, wherein R⁵ is alkyl substituted with aryl or heteroaryl, either of which may be optionally substituted with 1 to 3 R¹⁰.

6. The compound according to claim 1, wherein:

R¹ is selected from the group consisting of aryl and heteroaryl, either of which may be optionally substituted with 1 to 3 R¹⁰;

R² is aryl which may be optionally substituted with 1 to 3 R¹⁰;

R³ is selected from the group consisting of hydrogen and alkyl;

R⁴ is selected from the group consisting of hydrogen and alkyl; and

R⁵ is alkyl substituted with aryl or heteroaryl, either of which may be optionally substituted with 1 to 3 R¹⁰.

7. The compound according to claim 1, wherein:

R¹ is selected from the group consisting of hydrogen and alkyl;

R² is aryl which may be optionally substituted with 1 to 3 R¹⁰;

R³ is selected from the group consisting of aryl and heteroaryl, either of which may be optionally substituted with 1 to 3 R¹⁰;

R⁴ is selected from the group consisting of hydrogen and alkyl; and

R⁵ is alkyl substituted with aryl or heteroaryl, either of which may be optionally substituted with 1 to 3 R¹⁰.

8. The compound according to claim 1, wherein:

R¹ is aryl which may be optionally substituted with 1 to 3 R¹⁰;

R² is selected from the group consisting of aryl and heteroaryl, either of which may be optionally substituted with 1 to 3 R¹⁰;

R³ is selected from the group consisting of hydrogen and alkyl;

R⁴ is selected from the group consisting of hydrogen and alkyl; and

R⁵ is alkyl substituted with aryl or heteroaryl, either of which may be optionally substituted with 1 to 3 R¹⁰.

9. The compound according to claim 1, wherein:

R¹ is selected from the group consisting of hydrogen and alkyl;

R² is selected from the group consisting of aryl and heteroaryl, either of which may be optionally substituted with 1 to 3 R¹⁰;

R³ is aryl which may be optionally substituted with 1 to 3 R¹⁰;

R⁴ is selected from the group consisting of hydrogen and alkyl; and

R⁵ is alkyl substituted with aryl or heteroaryl, either of which may be optionally substituted with 1 to 3 R¹⁰.

10. The compound according to claim 1, wherein the compound is selected from the group consisting of:

11. The compound according to claim 1, wherein the compound is selected from the group consisting of:

12. A pharmaceutical composition, comprising:

at least one compound according to claim 1;

and at least one pharmaceutically acceptable carrier or diluent.

13. The pharmaceutical composition according to claim 12, further comprising:

at least one additional therapeutic agent.

14. A pharmaceutical combination comprising a pharmaceutical composition of claim 12 and a therapeutic agent selected from anti-obesity agents;

appetite suppressants;

anti-diabetic agents;

anti-hyperlipidemia agents;

hypolipidemic agents;

hypocholesterolemic agents;

lipid-modulating agents;

cholesterol-lowering agents;

lipid-lowering agents;

HDL-raising agent, anti-hypertensive agents;

agents used to treat sleep disorders;

agents used to treat substance abuse and addictive disorders;

anti-anxiety agents;

anti-depressants;

anti-psychotic agents;

cognition enhancing agents;

agents used to treat cognitive disorders;

agents used to treat Alzheimer'"'"'s disease;

agents used to treat Parkinson'"'"'s disease;

anti-inflammatory agents;

agents used to treat neurodegeneration;

agents used to treat arteriosclerosis;

agents used to treat respiratory conditions;

agents used to treat bowel disorders;

cardiac glycosides; and

anti-tumor agents.

15. The pharmaceutical combination according to claim 14 wherein the other therapeutic agent may be administered prior to, simultaneously with, or following the administration of the pharmaceutical composition of claim 12.

16. A method for treating obesity, comprising:

administering a therapeutically effective amount of at least one cannabinoid receptor 1 antagonist according to claim 1 to a patient in need.

17. A method for smoking cessation, comprising:

administering a therapeutically effective amount of at least one cannabinoid receptor 1 antagonist according to claim 1 to a patient in need.