Benzodiazepine calcitonin gene-related peptide (CGRP) receptor antagonists: Optimization of the 4-substituted piperidine

被引：44

作者：

Burgey, Christopher S. ^{[1
]}

Stump, Craig A.

Nguyen, Diem N.

Deng, James Z.

Quigley, Amy G.

Norton, Beth R.

Bell, Ian M.

Mosser, Scott D.

Salvatore, Christopher A.

Rutledge, Ruth Z.

Kane, Stefanie A.

Koblan, Kenneth S.

Vacca, Joseph P.

Graham, Samuel L.

Williams, Theresa M.

机构：

[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA

[2] Merck Res Labs, Dept Pain Res, West Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 19期

关键词：

CGRP; antagonist; migraine;

D O I：

10.1016/j.bmcl.2006.07.044

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In our continuing effort to identify CGRP receptor antagonists for the acute treatment of migraine, we have undertaken a study to evaluate alternative 4-substituted piperidines to the lead dihydroquinazolinone 1. In this regard, we have identified the piperidinyl-azabenzimidazolone and phenylimidazolinone structures which, when incorporated into the benzodiazepine core, afford potent CGRP receptor antagonists (e.g., 18 and 29). These studies produced a potent analog (18) which overcomes the instability issues associated with the lead structure 1. A general pharmacophore for the 4-substituted piperidine component of these CGRP receptor antagonists is also presented. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：5052 / 5056

页数：5

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