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

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• 作者：Guanglin Luo ; ^{guanglin.luo@bms.com} ; Ling Chen ; Rita Civiello ; Sokhom S. Pin ; Cen Xu ; Walter Kostich ; Michelle Kelley ; Charles M. Conway ; John E. Macor ; Gene M. Dubowchik
• 关键词：CGRP antagonist ; Migraine
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：15 April, 2012
• 卷：22
• 期：8
• 页码：2917-2921
• 文件大小：1290 K

摘要

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.