Carbamates as potent calcitonin gene-related peptide antagonists with improved solution stability

The calcitonin gene-related peptide (CGRP) receptor has been implicated in the pathogenesis of migraine. A class of urethanamide derivatives has been identified as potent inhibitors of the CGRP receptor. Compound 20 was found to be among the most potent (IC50 = 17 pM). It was shown to retain excellent aqueous solubility (>50 mg/mL, pH 7) while dramatically improving solution stability as compared to our previously disclosed development candidate, BMS-694153 (1).

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