Novel oxazolidinone calcitonin gene-related peptide (CGRP) receptor antagonists for the acute treatment of migraine. Issue 21 (1st November 2015) - Crowley, Brendan M.
Graphical abstract: 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 IC50 = 0.67 nM), and selective compound (hERG IC50 = 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).