Design, synthesis and evaluation of bicyclic benzamides as novel 5-HT1F receptor agonists

被引：17

作者：

Zhang, DY ^{[1
]}

Kohlman, D

Krushinski, J

Liang, S

Ying, BP

Reilly, JE

Dinn, SR

Wainscott, DB

Nutter, S

Gough, W

Nelson, DLG

Schaus, JM

Xu, YC

机构：

[1] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA

[2] Albany Mol Res, Albany, NY 12212 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 24期

关键词：

5-HT1F receptor agonist; migraine;

D O I：

10.1016/j.bmcl.2004.09.079

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several fused bicyclic systems have been investigated to serve as the core structure of potent and selective 5-HT1F receptor agonists. Replacement of the indole nucleus in 2 with indazole and 'inverted' indazole provided more potent and selective 5-HT1F receptor ligands. Indoline and 1,2-benzisoxazole systems also provided potent 5-HT1F receptor agonists, and the 5-HT1A receptor selectivity of the indoline- and 1,2-benzisoxazole-based 5-HT1F receptor agonists could be improved with modification of the benzoyl moiety of the benzamides. Through these studies, we found that the inherent geometries of the templates, not the nature of hybridization of the linking atom, were important for the 5-HT1F receptor recognition. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：6011 / 6016

页数：6

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