Discovery of Potent and Selective Urea-Based ROCK Inhibitors and Their Effects on Intraocular Pressure in Rats

被引：39

作者：

Yin, Yan ^{[1
,2
]}

Cameron, Michael D. ^{[1
,2
]}

Lin, Li ^{[1
,2
]}

Khan, Susan ^{[1
,2
]}

Schroeter, Thomas ^{[1
,2
]}

Grant, Wayne ^{[1
,2
]}

Pocas, Jennifer ^{[1
,2
]}

Chen, Yen Ting ^{[1
,2
]}

Schuerer, Stephan ^{[3
,4
]}

Pachori, Alok ^{[1
,2
]}

LoGrasso, Philip ^{[1
,2
]}

Feng, Yangbo ^{[1
,2
]}

机构：

[1] Translat Res Inst, Jupiter, FL 33458 USA

[2] Dept Mol Therapeut, Jupiter, FL 33458 USA

[3] Univ Miami, Dept Pharmacol, Miami, FL 33136 USA

[4] Univ Miami, Ctr Computat Sci, Miami, FL 33136 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2010年 / 1卷 / 04期

关键词：

Glaucoma; ROCK; IOP; kinase inhibitor; urea; pyrazole; PROTEIN-KINASE INHIBITOR; RHO; PHOSPHORYLATION;

D O I：

10.1021/ml1000382

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of urea-based Rho kinase (ROCK) inhibitors were designed and evaluated. The discovered compounds had excellent enzyme and cellular potency, high kinase selectivity, high aqueous solubility, good porcine corneal penetration, and appropriate DMPK profiles for topical applications as antiglaucoma therapeutics.

引用

页码：175 / 179

页数：5

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