Trisubstituted ureas as potent and selective mPGES-1 inhibitors

被引：23

作者：

Chiasson, Jean-Francois ^{[1
]}

Boulet, Louise ^{[1
]}

Brideau, Christine ^{[1
]}

Chau, Anh ^{[1
]}

Claveau, David ^{[1
]}

Cote, Bernard ^{[1
]}

Ethier, Diane ^{[1
]}

Giroux, Andre ^{[1
]}

Guay, Jocelyne ^{[1
]}

Guiral, Sebastien ^{[1
]}

Mancini, Joseph ^{[1
]}

Masse, Frederic ^{[1
]}

Methot, Nathalie ^{[1
]}

Riendeau, Denis ^{[1
]}

Roy, Patrick ^{[1
]}

Rubin, Joel ^{[1
]}

Xu, Daigen ^{[1
]}

Yu, Hongping ^{[1
]}

Ducharme, Yves ^{[1
]}

Friesen, Richard W. ^{[1
]}

机构：

[1] Merck Frosst Ctr Therapeut Res, Kirkland, PQ H9H 3L1, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 05期

关键词：

mPGES-1; PGE synthase; Inflammation; Prostaglandins; Trisubstituted urea; PROSTAGLANDIN-E SYNTHASE; E-2; SYNTHASE; PAIN;

D O I：

10.1016/j.bmcl.2011.01.006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of trisubstituted ureas has been identified as potent and selective mPGES-1 inhibitors. These compounds are selective over other prostanoid enzymes such as PGF synthase and TX synthase. This series of inhibitors was developed by lead optimization of a hit from an internal HTS campaign. Lead compound 42 is potent in A549 cell assay (IC50 of 0.34 mu M) and in human whole blood assay (IC50 of 2.1 mu M). An efficient and versatile one-pot strategy for the formation of ureas, involving a reductive amination, was developed to generate these inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1488 / 1492

页数：5

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