Abstract
The identification of a new class of potent and selective ROCK-II inhibitors is presented. Compound 5 (SR-3677) had an IC 50 of approximately 3 nM in enzyme and cell based assays and had an off-target hit rate of 1.4% against 353 kinases, and inhibited only 3 out of 70 nonkinase enzymes and receptors. Pharmacology studies showed that 5 was efficacious in both, increasing ex vivo aqueous humor outflow in porcine eyes and inhibiting myosin light chain phosphorylation.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacology*
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Animals
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Dioxanes / chemistry*
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Drug Evaluation, Preclinical
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Models, Molecular
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Molecular Structure
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology*
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Pyrazoles / chemistry*
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Rats
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Structure-Activity Relationship
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Swine
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rho-Associated Kinases / antagonists & inhibitors*
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rho-Associated Kinases / metabolism
Substances
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Amides
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Dioxanes
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Protein Kinase Inhibitors
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Pyrazoles
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pyrazole
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rho-Associated Kinases