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

…, R Civiello, SS Pin, C Xu, W Kostich, M Kelley…

Index: Luo, Guanglin; Chen, Ling; Civiello, Rita; Pin, Sokhom S.; Xu, Cen; Kostich, Walter; Kelley, Michelle; Conway, Charles M.; MacOr, John E.; Dubowchik, Gene M. Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 8 p. 2917 - 2921

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Citation Number: 10

Abstract

In our continuing efforts to identify CGRP receptor antagonists that can be dosed orally for the treatment of migraine headache, we have investigated a pyridine bioisosteric replacement of a polar amide portion of a previous lead compound, BMS-694153. Pyridine derivatives were discovered and their SAR was studied. Some of them showed excellent binding potency. However, oral bioavailability was low, even for compounds with good ...