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

Christopher W Plummer; 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

doi:10.1016/j.bmcl.2004.12.078

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.

Authors

Christopher W Plummer¹, 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

Affiliation

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.

MeSH terms

Animals
Area Under Curve
Binding, Competitive / drug effects
Body Weight / drug effects
Disease Models, Animal
Drug Evaluation, Preclinical
Eating / drug effects
Humans
Imidazoles / chemical synthesis*
Imidazoles / pharmacokinetics
Imidazoles / pharmacology*
Molecular Structure
Obesity / drug therapy*
Rats
Receptor, Cannabinoid, CB1 / drug effects*
Structure-Activity Relationship

Substances

Imidazoles
Receptor, Cannabinoid, CB1