Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Rd., PO Box 368, Ridgefield, CT 06877-036, USA.
Bioorg Med Chem Lett. 2013 Apr 1;23(7):2177-80. doi: 10.1016/j.bmcl.2013.01.105. Epub 2013 Feb 4.
Potent small molecule antagonists of the urotensin receptor are described. These inhibitors were derived via systematically deconstructing a literature inhibitor to understand the basic pharmacophore and key molecular features required to inhibit the protein receptor. The series of benzylamine and benzylsulfone antagonists herein reported display a combination of nanomolar molecular and cellular potency as well as acceptable in vitro permeability and metabolic stability.
本文描述了几种对尿皮质素受体具有强效抑制作用的小分子拮抗剂。这些抑制剂是通过系统地解构文献抑制剂来了解基本的药效团和抑制蛋白受体所需的关键分子特征而衍生出来的。本文报道的一系列苄胺和苄砜类拮抗剂具有纳摩尔级别的分子和细胞活性，以及可接受的体外渗透性和代谢稳定性。
