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

2012; Elsevier BV; Volume: 22; Issue: 8 Linguagem: Inglês

10.1016/j.bmcl.2012.02.065

1464-3405

Guanglin Luo, Ling Chen, Rita L. Civiello, Sokhom S. Pin, Cen Xu, Walter A. Kostich, Michelle Kelley, Charles M. Conway, John E. Macor, Gene M. Dubowchik,

Trigeminal Neuralgia and Treatments

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 Caco-2 cell permeability.