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.

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

来源：Bioorganic & medicinal chemistry letters 2016 年 26卷 4期