Substituted azole aromatic heterocycles as inhibitors of 11β-HSD-1

• US 7,666,888 B2
• Filed: 07/18/2007
• Issued: 02/23/2010
• Est. Priority Date: 07/20/2006
• Status: Expired due to Fees

• Current Assignee: Amgen Inc., Biovitrum AB (Swedish Orphan Biovitrum AB (publ))
• Original Assignee: Amgen Inc., Biovitrum AB (Swedish Orphan Biovitrum AB (publ))
• Inventors: Fotsch, Christopher H., St. Jean, David, Flyren, Katrina, Sutin, Lori, Bartberger, Michael D., Johansson, Lars, Nilsson, Marianne, Haraldsson, Martin
• Primary Examiner(s): Saeed; Kamal A
• Assistant Examiner(s): BIANCHI, KRISTIN A
• Application Number:
  US11/779,599
• Publication Number:
  US 20080021022A1
• Time in Patent Office: 951 Days
• Field of Search: 544/137, 544/367, 544/405, 544/60, 546/17, 546/208, 546/272.1, 548/248, 514/227.8, 514/236.8, 514/254.04, 514/255.05, 514/326, 514/340, 514/378
• US Class Current: 514/378
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• 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: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links

Abstract

Compounds of formula I and IV are described and have therapeutic utility, particularly in the treatment of diabetes, obesity and related conditions and disorder:

wherein the variables A-B, R¹, R², m, and Q are described herein.

Claims

1. A compound according to formula I, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof:

2. The compound according to claim 1, or a stereoisomer, tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R² is selected from the group consisting of C_1-8-alkyl, C_1-6-haloalkyl, and aryl.

3. The compound according to claim 2, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R² is selected from the group consisting of CH₃, CF₃, and optionally substituted phenyl.

4. The compound according to claim 1, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein ring Q is formula IIa:

5. The compound according to claim 4, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein:

R¹ is selected from the group consisting of H, F, Cl, Br, NO₂, and CH₃;

R³ is H;

R⁴ is aryl and heteroaryl;

R⁵ is H; and

m is 1.

6. The compound according to claim 5, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R⁴ is selected from the group consisting of optionally substituted phenyl, 2-pyridyl, 3-pyridyl, and 4-pyridyl.

7. The compound according to claim 1, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is of the formula I-IIb:

8. The compound according to claim 7, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein:

n is 0, and

R² is H.

9. The compound according to claim 1, wherein A-B represents N(H)—

N.

10. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

11. A compound that is selected from the following table:

14. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 11, 12 or 13, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

12. A compound that is selected from the following table:

13. A compound that is selected from the following table: