Synthesis and SAR of calcitonin gene-related peptide (CGRP) antagonists containing substituted aryl-piperazines and piperidines.

Calcitonin gene-related peptide(CGRP) is a potent neuropeptideimplicated 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 piperidineand piperazineanalogs of BMS-694153 were prepared. Several were found to have nM binding affinity in vitro. The synthesis and SAR of these substituted piperidineand piperazineCGRP antagonists are discussed.