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ID: ALA1149490
Journal: Bioorg Med Chem Lett
Title: SAR of biphenyl carboxamide ligands of the human melanin-concentrating hormone receptor 1 (MCH R1): discovery of antagonist SB-568849.
Authors: Witty DR, Bateson JH, Hervieu GJ, Jeffrey P, Johnson CN, Muir AI, O'Hanlon PJ, Stemp G, Stevens AJ, Thewlis KM, Wilson S, Winborn KY.
Abstract: We report here the discovery of a class of MCH R1 ligands based on a biphenyl carboxamide template. A docked-in model is presented indicating key interactions in the putative binding site of the receptor. Parallel high throughput synthetic techniques were utilised to allow rapid exploration of the structure-activity relationship around this template, leading to compound SB-568849 which possessed good receptor affinity and selectivity. This compound proved to be an antagonist with stability in vivo, an acceptable brain-blood ratio and oral bioavailability.
CiteXplore: 16839761