Synthesis and SAR of calcitonin gene-related peptide (CGRP) antagonists containing substituted aryl-piperazines and piperidines
详细信息 查看全文
- 作者：Rita L. Civiello ; Xiaojun Han ; Brett R. Beno ; Prasad V. Chaturvedula ; John J. Herbst ; Cen Xu ; Charles M. Conway ; John E. Macor ; Gene M. Dubowchik
- 关键词：CGRP receptor antagonist ; Calcitonin gene-related peptide (CGRP) ; Migraine headache
- 刊名：Bioorganic & Medicinal Chemistry Letters
- 出版年：2016
- 出版时间：15 February 2016
- 年：2016
- 卷：26
- 期：4
- 页码：1229-1232
- 全文大小：844 K
文摘
Calcitonin gene-related peptide (CGRP) is a potent neuropeptide implicated in the pathophysiology of migraine. In the course of seeking CGRP antagonists with improved oral bioavailability, metabolic stability, and pharmacokinetic properties, lower molecular weight, structurally simpler piperidine and piperazine analogs of BMS-694153 were prepared. Several were found to have nM binding affinity in vitro. The synthesis and SAR of these substituted piperidine and piperazine CGRP antagonists are discussed.