(E)-Alkenes as replacements of amide bonds: Development of novel and potent acyclic CGRP receptor antagonists

被引：6

作者：

Kim, June J. ^{[1
]}

Wood, Michael R. ^{[1
]}

Stachel, Shawn J. ^{[1
]}

de Leon, Pablo ^{[1
]}

Nomland, Ashley ^{[1
]}

Stump, Craig A. ^{[1
]}

McWherter, Melody A. ^{[1
]}

Schirripa, Kathy M. ^{[1
]}

Moore, Eric L. ^{[2
]}

Salvatore, Christopher A. ^{[2
]}

Selnick, Harold G. ^{[1
]}

机构：

[1] Merck & Co Inc, Dept Med Chem, West Point, PA 19486 USA

[2] Merck & Co Inc, Dept Pain Res, West Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 01期

关键词：

CGRP; Migraine; (E)-Alkene; P-gp; MIGRAINE;

D O I：

10.1016/j.bmcl.2013.11.027

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new class of CGRP receptor antagonists was identified by replacing the central amide of a previously identified anilide lead structure with ethylene, ethane, or ethyne linkers. (E)-Alkenes as well as alkynes were found to preserve the proper bioactive conformation of the amides, necessary for efficient receptor binding. Further exploration resulted in several potent compounds against CGRP-R with low susceptibility to P-gp mediated efflux. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：258 / 261

页数：4

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