Novel oxazolidinone calcitonin gene-related peptide (CGRP) receptor antagonists for the acute treatment of migraine

Abstract In our efforts to develop CGRP receptor antagonists as backups to MK-3207, 2 , we employed a scaffold hopping approach to identify a series of novel oxazolidinone-based compounds. The development of a structurally diverse, potent ( 20 , cAMP + HS IC 50  = 0.67 nM), and selective compound (hERG IC 50  = 19 μM) with favorable rodent pharmacokinetics ( F  = 100%, t 1/2  = 7 h) is described. Key to this development was identification of a 3-substituted spirotetrahydropyran ring that afforded a substantial gain in potency (10 to 35-fold).