Novel benzoxazole inhibitors of mPGES-1

被引：25

作者：

Kablaoui, Natasha ^{[1
]}

Patel, Snahel ^{[2
]}

Shao, Jay ^{[1
]}

Demian, Douglas ^{[3
]}

Hoffmaster, Keith ^{[4
]}

Berlioz, Francioise ^{[5
]}

Vazquez, Michael L. ^{[6
]}

Moore, William M. ^{[7
]}

Nugent, Richard A. ^{[1
]}

机构：

[1] Pfizer Res Technol Ctr, Cambridge, MA 02139 USA

[2] Genentech Inc, San Francisco, CA 94080 USA

[3] Blue Sky Biotech Inc, Worcester, MA 01605 USA

[4] Novartis Inc, Cambridge, MA 02139 USA

[5] Vertex, Cambridge, MA 02139 USA

[6] Pfizer Global Res, Groton, CT 06340 USA

[7] Monsanto Co, St Louis, MO 63167 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 03期

关键词：

mPGES-1; Benzoxazole; Selective; PROSTAGLANDIN-E SYNTHASE-1; EXPRESSION; ARTHRITIS; CARTILAGE; PYRESIS;

D O I：

10.1016/j.bmcl.2012.10.040

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of potent benzoxazole mPGES-1 inhibitors has been derived from a hit from a high throughput screen. Compound 37 displays mPGES-1 inhibition in an enzyme assay (0.018 mu M) and PGE-2 inhibition in a cell-based assay (0.034 mu M). It demonstrates 500- and 2500-fold selectivity for mPGES-1 over COX-2 and 6-keto PGF-1 alpha, respectively. In vivo PK studies in dogs demonstrate 55% oral bioavailability and an 7 h half-life. (c) 2012 Elsevier Ltd. All rights reserved.

引用

页码：907 / 911

页数：5

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