Identification of potent CNS-penetrant thiazolidinones as novel CGRP receptor antagonists

Calcitonin gene-related peptide (CGRP) has been implicated in acute migraine pathogenesis. In an effort to identify novel CGRP receptor antagonists for the treatment of migraine, we have discovered thiazolidinone 49, a potent (Ki = 30 pM, IC50 = 1 nM), orally bioavailable, CNS-penetrant CGRP antagonist with good pharmacokinetic properties.