Potent benzimidazolone-based CGRP receptor antagonists

被引：12

作者：

Theberge, Cory R. ^{[1
]}

Bednar, Rodney A. ^{[1
]}

Bell, Ian M. ^{[1
]}

Corcoran, Halea A. ^{[3
]}

Fay, John F. ^{[1
]}

Hershey, James C. ^{[3
]}

Johnston, Victor K. ^{[2
]}

Kane, Stefanie A. ^{[2
]}

Mosser, Scott ^{[1
]}

Salvatore, Christopher A. ^{[2
]}

Williams, Theresa M. ^{[1
]}

Zartman, C. Blair ^{[1
]}

Zhang, Xu-Fang ^{[1
]}

Graham, Samuel L. ^{[1
]}

Vacca, Joseph P. ^{[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

[3] Merck & Co Inc, Dept Bone Resp Immunol & Endocrine, West Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 23期

关键词：

Migraine; CGRP; Spirohydantoin; Benzimidazole;

D O I：

10.1016/j.bmcl.2008.10.019

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The previously disclosed spirohydantoin-based CGRP receptor antagonists were optimized for potency through modi. cation of the benzimidazolone substituents. Compounds were identified which had minimal shift in the cAMP functional assay containing 50% human serum. Blockade of CGRP-mediated vasodilation was observed with these compounds in a rhesus pharmacodynamic assay and the in vivo potency correlated with the in vitro activity in the serum-shifted functional assay. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：6122 / 6125

页数：4

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