Discovery and optimization of highly ligand-efficient oxytocin receptor antagonists using structure-based drug design

被引：14

作者：

Bellenie, Benjamin R. ^{[1
]}

Barton, Nicholas P. ^{[1
]}

Emmons, Amanda J. ^{[1
]}

Heer, Jag P. ^{[1
]}

Salvagno, Cristian ^{[2
]}

机构：

[1] GlaxoSmithKline Inc, Harlow CM19 5AD, Essex, England

[2] GlaxoSmithKline SpA, Med Res Ctr, Verona, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 03期

关键词：

Oxytocin antagonist; Cresset FieldScreen; Oxytocin; Vasopressin; Molecular field; Hit discovery; Structure-based drug design; PRETERM; POTENT; LABOR;

D O I：

10.1016/j.bmcl.2008.11.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel oxytocin antagonist was identified by 'scaffold-hopping' using Cresset FieldScreen molecular field similarity searching. A single cycle of optimization driven by an understanding of the key pharmacophoric elements required for activity led to the discovery of a potent, selective and highly ligand-efficient oxytocin receptor antagonist. Selectivity over vasopressin receptors was rationalized based on differences in the structure of the natural ligands. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：990 / 994

页数：5

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