Calcitonin gene-related peptide (CGRP) receptor antagonists: pyridine as a replacement for a core amide group.

Abstract In our continuing efforts to identify CGRP receptorantagonists that can be dosed orally for the treatment of migraine headache, we have investigated a pyridine bioisostericreplacement of a polar amide portion of a previous lead compound, BMS-694153. Pyridinederivatives were discovered and their SAR was studied. Some of them showed excellent binding potency. However, oral bioavailability was low, even for compounds with good Caco-2cell permeability.