Abstract
Inhibitors of Rho kinase have been developed based on two distinct scaffolds, benzimidazoles, and benzoxazoles. SAR studies and efforts to optimize the initial lead compounds are described. Novel selective inhibitors of ROCK-II with excellent potency in both enzyme and cell-based assays were obtained. These inhibitors possess good microsomal stability, low cytochrome P-450 inhibitions and good oral bioavailability.
MeSH terms
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacology*
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Benzoxazoles / chemistry
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Benzoxazoles / pharmacology*
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Chemistry, Pharmaceutical / methods*
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Chromans / chemistry
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Drug Design
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Glaucoma / drug therapy
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Humans
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Hypertension / drug therapy
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Inhibitory Concentration 50
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Microsomes / drug effects
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Microsomes, Liver / metabolism
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Models, Chemical
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Pyrazoles / chemistry
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Pyrimidines / chemistry
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rho-Associated Kinases / antagonists & inhibitors*
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rho-Associated Kinases / chemistry
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rho-Associated Kinases / metabolism
Substances
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Benzimidazoles
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Benzoxazoles
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Chromans
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Pyrazoles
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Pyrimidines
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rho-Associated Kinases