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Bioorg Med Chem Lett. 2007 May 15;17(10):2706-11. Epub 2007 Mar 12.

Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity.

Author information

1
Department of Chemistry Research, Bayer HealthCare, Pharmaceuticals Division, West Haven, CT 06516, USA. rosmith@angio.com

Abstract

Several imidazole-based cyclohexyl amides were identified as potent CB-1 antagonists, but they exhibited poor oral exposure in rodents. Incorporation of a hydroxyl moiety on the cyclohexyl ring provided a dramatic improvement in oral exposure, together with a ca. 10-fold decrease in potency. Further optimization provided the imidazole 2-hydroxy-cyclohexyl amide 45, which exhibited hCB-1 K(i)=3.7nM, and caused significant appetite suppression and robust, dose-dependent reduction of body weight gain in industry-standard rat models.

PMID:
17383180
DOI:
10.1016/j.bmcl.2007.03.011
[Indexed for MEDLINE]

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