Rapid synthesis of an array of trisubstituted urea-based soluble epoxide hydrolase inhibitors facilitated by a novel solid-phase method

被引：13

作者：

Kowalski, Jennifer A. ^{[1
]}

Swinamer, Alan D. ^{[1
]}

Muegge, Ingo ^{[1
]}

Eldrup, Anne B. ^{[1
]}

Kukulka, Alison ^{[1
]}

Cywin, Charles L. ^{[1
]}

De Lombaert, Stephane ^{[1
]}

机构：

[1] Boehringer Ingelheim Pharmaceut Inc, Dept Med Chem, Ridgefield, CT 06877 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 12期

关键词：

Parallel array; Soluble epoxide hydrolase; Solid-phase synthesis; EPOXYEICOSATRIENOIC ACIDS; TRACELESS SYNTHESIS; HIGHLY POTENT; DISCOVERY; REVEALS;

D O I：

10.1016/j.bmcl.2010.04.078

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A 270-membered library of trisubstituted ureas was synthesized and evaluated for inhibition of soluble epoxide hydrolase. Library design and reagent selection was guided by the use of a pharmacophore model and synthesis of the array was enabled with a general solid-phase method. This array approach facilitated multi-dimensional SAR around this series and identified functionality responsible for binding affinity, as well as opportunities for modulating the overall in vitro profiles of this class of soluble epoxide hydrolase inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：3703 / 3707

页数：5

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