Synthesis and activity of 4,5-diarylimidazoles as human CB1 receptor inverse agonists

  • Bioorg Med Chem Lett. 2005 Mar 1;15(5):1441-6. doi: 10.1016/j.bmcl.2004.12.078.
Christopher W Plummer  1 ,  Paul E Finke ,  Sander G Mills ,  Junying Wang ,  Xinchun Tong ,  George A Doss ,  Tung M Fong ,  Julie Z Lao ,  Marie-Therese Schaeffer ,  Jing Chen ,  Chun-Pyn Shen ,  D Sloan Stribling ,  Lauren P Shearman ,  Alison M Strack ,  Lex H T Van der Ploeg
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. [email protected]
PMID: 15713403 DOI: 10.1016/j.bmcl.2004.12.078
Abstract

Structure-activity relationship studies directed toward the optimization of 4,5-diarylimidazole-2-carboxamide analogs as human CB1 receptor inverse agonists resulted in the discovery of the two amide derivatives 24a and b (hCB1 IC50 = 6.1 and 4.0 nM) which also demonstrated efficacy in overnight feeding studies in the rat for reduction in both food intake and overall body weight.