Chen Caroline W, Tran Joe A, Fleck Beth A, Tucci Fabio C, Jiang Wanlong, Chen Chen
Department of Medicinal Chemistry, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Bioorg Med Chem Lett. 2007 Dec 15;17(24):6825-31. doi: 10.1016/j.bmcl.2007.10.032. Epub 2007 Oct 17.
A series of trans-N-alkyl-4-(4-chlorophenyl)pyrrolidine-3-carboxamides of piperazinecyclohexanemethylamines was synthesized and characterized for binding and function at the melanocortin-4 receptor (MC4R), and several potent benzylamine derivatives were identified. Compound 18 v was found to bind MC4R with potent affinity (K(i)=0.5 nM) and high selectivity over the other melanocortin subtypes and behaved as a functional antagonist (IC(50)=48 nM).
合成了一系列哌嗪环己甲胺的反式-N-烷基-4-(4-氯苯基)吡咯烷-3-甲酰胺，并对其在黑皮质素-4受体(MC4R)上的结合和功能进行了表征，鉴定出了几种有效的苄胺衍生物。发现化合物18 v以强效亲和力(K(i)=0.5 nM)结合MC4R，对其他黑皮质素亚型具有高选择性，并且表现为功能性拮抗剂(IC(50)=48 nM)。
