Journal of Medicinal Chemistry · 2006 · 71 citations · 3 references
PharmacyMedicinal ChemistryPharmacologyDrug DesignDrug DiscoveryLead OptimizationHypertension ManagementHypertension PharmacotherapyLigand-based DesignPharmacokinetic OptimizationPotency OptimizationStructure-activity Relationship AnalysisAntihypertensive Drug TherapyBinding Mode AnalysisBinding Mode OptimizationBlood PressureDrug Candidate OptimizationEnzyme Activity PotencyKinase InhibitorsProtein Kinase Inhibitors
The discovery, proposed binding mode, and optimization of a novel class of Rho-kinase inhibitors are presented. Appropriate substitution on the 6-position of the azabenzimidazole core provided subnanomolar enzyme potency in vitro while dramatically improving selectivity over a panel of other kinases. Pharmacokinetic data was obtained for the most potent and selective examples and one (6n) has been shown to lower blood pressure in a rat model of hypertension.
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Copper-Catalyzed Coupling of Aryl Iodides with Aliphatic Alcohols
Martina Wolter, Gero Nordmann, Gabriel E. Job et al. · Organic Letters · 2002 · 384 citations