Obesity Research Today is a free monthly online journal that collates and summarizes the latest research about Obesity, including details on health, diet, prevention, exercise.

Identification of 2-(4-benzyloxyphenyl)-N- [1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-6-yl]acetamide, an orally efficacious melanin-concentrating hormone receptor 1 antagonist for the treatment of obesity.

Souers AJ, Gao J, Brune M, Bush E, Wodka D, Vasudevan A, Judd AS, Mulhern M, Brodjian S, Dayton B, Shapiro R, Hernandez LE, Marsh KC, Sham HL, Collins CA, Kym PR

Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. andrew.souers@abbott.com

Optimization of a high-throughput screening hit against melanin-concentrating hormone receptor 1 (MCHr1) led to the discovery of 2-(4-benzyloxy-phenyl)-N-[1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-6-yl]acetamide (7a). This compound was found to be a high-affinity ligand for MCHr1 and a potent inhibitor of MCH-mediated Ca(2+) release, showed good plasma and CNS exposure upon oral dosing in diet-induced obese mice, and is the first reported MCHr1 antagonist that is efficacious upon oral dosing in a chronic model of weight loss.

Published 3 March 2005 in J Med Chem, 48(5): 1318-21.
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