发现取代的（4-苯基-1H-咪唑-2-基）甲胺作为有效的生长抑素受体3激动剂。

Discovery of substituted (4-phenyl-1H-imidazol-2-yl)methanamine as potent somatostatin receptor 3 agonists.

作者信息

Lai Zhong, He Shuwen, Sherer Edward C, Wu Zhicai, Yu Yang, Ball Richard, Hong Qingmei, Yang David X, Guo Liangqing, Li Derun, Tuang Quang, Chicchi Gary G, Trusca Dorina, Tsao Kwei-Lan, Zhou Yun-Ping, Howard Andrew D, Nargund Ravi P, Hagmann William K

机构信息

Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 539, Kenilworth, NJ 07033, USA.

出版信息

Bioorg Med Chem Lett. 2015 Sep 1;25(17):3520-5. doi: 10.1016/j.bmcl.2015.06.087. Epub 2015 Jul 4.

DOI:10.1016/j.bmcl.2015.06.087

PMID:26199120

Abstract

We report SAR studies on a novel non-peptidic somatostatin receptor 3 (SSTR3) agonist lead series derived from (4-phenyl-1H-imidazol-2-yl)methanamine. This effort led to the discovery of a highly potent low molecular weight SSTR3 agonist 5c (EC50=5.2 nM, MW=359). The results from molecular overlays of 5c onto the L-129 structure indicate good alignment, and two main differences of the proposed overlays of the antagonist MK-4256 onto the conformation of 5c lead to inversion of antagonism to agonism.

摘要

我们报告了对源自（4-苯基-1H-咪唑-2-基）甲胺的新型非肽类生长抑素受体3（SSTR3）激动剂先导系列的构效关系研究。这项工作导致发现了一种高效的低分子量SSTR3激动剂5c（EC50 = 5.2 nM，分子量 = 359）。将5c与L-129结构进行分子叠加的结果表明二者匹配良好，并且拮抗剂MK-4256与5c构象的拟叠加结构的两个主要差异导致了拮抗作用向激动作用的转变。