Benzothiophene containing Rho kinase inhibitors: Efficacy in an animal model of glaucoma

被引：23

作者：

Davis, Robert L. ^{[1
]}

Kahraman, Mehmet ^{[1
,3
]}

Prins, Thomas J. ^{[1
]}

Beaver, Yan ^{[1
]}

Cook, Travis G. ^{[1
]}

Cramp, Jessica ^{[1
]}

Cayanan, Charmagne S. ^{[1
]}

Gardiner, Elisabeth M. M. ^{[1
]}

McLaughlin, Marsha A. ^{[2
]}

Clark, Abbot F. ^{[2
]}

Hellberg, Mark R. ^{[2
]}

Shiau, Andrew K. ^{[1
]}

Noble, Stewart A. ^{[1
]}

Borchardt, Allen J. ^{[1
]}

机构：

[1] Kalypsys Inc, San Diego, CA 92121 USA

[2] Alcon Res Ltd, Ft Worth, TX 76134 USA

[3] Aragon Pharmaceut Inc, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 11期

关键词：

ROCK; Rho; Kinase; Adhesion; Impedance; Benzothiophene; ATP competitive; Inhibitor; Glaucoma; AQUEOUS-HUMOR OUTFLOW; PROTEIN-KINASE; TRABECULAR MESHWORK; ROCK INHIBITORS; PATHWAY; Y-27632; PHOSPHORYLATION; CONTRACTION; MODULATION; ACTIVATION;

D O I：

10.1016/j.bmcl.2010.04.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We identified a new benzothiophene containing Rho kinase inhibitor scaffold in an ultra high-throughput enzymatic activity screen. SAR studies, driven by a novel label-free cellular impedance assay, were used to derive 39, which substantially reduced intraocular pressure in a monkey model of glaucoma-associated ocular hypertension. (C) 2010 Elsevier Ltd. All rights reserved.

引用

收藏

页码：3361 / 3366

页数：6

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