Jacobs R T, Shenvi A B, Mauger R C, Ulatowski T G, Aharony D, Buckner C K
Department of Medicinal Chemistry, ZENECA Pharmaceuticals, Business Unit of ZENECA, Inc., Wilmington, DE 19850-5437, USA.
Bioorg Med Chem Lett. 1998 Jul 21;8(14):1935-40. doi: 10.1016/s0960-894x(98)00037-7.
A series of 4-alkylpiperidine derivatives related to the potent neurokinin-2 (NK2) receptor antagonist SR-48968 (1) is described. Simple aliphatic derivatives were found to be poorly active, but appropriate placement of an alcohol functional group afforded compounds that were of similar activity to 1. Several representatives in this series, such as the 4-(1-hydroxy-1-ethylpropyl)piperidine (14), were found to exhibit oral activity in a model of labored abdominal breathing in guinea pigs. These results expand the latitude of substituents available in this region of this series of NK2 receptor antagonists.
本文描述了一系列与强效神经激肽-2（NK2）受体拮抗剂SR-48968（1）相关的4-烷基哌啶衍生物。发现简单的脂肪族衍生物活性较差，但适当引入醇官能团可得到与1活性相似的化合物。该系列中的几个代表物，如4-(1-羟基-1-乙基丙基)哌啶（14），在豚鼠腹部呼吸困难模型中表现出口服活性。这些结果拓宽了该系列NK2受体拮抗剂这一区域可用取代基的范围。
