Abstract
The profile of a series of triazine and pyrimidine based ROCK inhibitors is described. An initial binding mode was established based on a homology model and the proposed interactions are consistent with the observed SAR. Compounds from the series are potent in a cell migration assay and possess a favorable kinase selectivity. In vivo activity was demonstrated for compound 1A in a spontaneous hypertensive rat model.
MeSH terms
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Animals
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Antihypertensive Agents / chemical synthesis
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Antihypertensive Agents / chemistry*
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Antihypertensive Agents / pharmacology
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Binding Sites
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Computer Simulation
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Disease Models, Animal
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Hypertension / drug therapy*
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry*
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Pyrimidines / pharmacology
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Rats
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Structure-Activity Relationship
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Triazines / chemical synthesis
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Triazines / chemistry*
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Triazines / pharmacology
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rho-Associated Kinases / antagonists & inhibitors*
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rho-Associated Kinases / metabolism
Substances
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Antihypertensive Agents
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Protein Kinase Inhibitors
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Pyrimidines
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Triazines
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rho-Associated Kinases