Discovery of Aminofurazan-azabenzimidazoles as Inhibitors of Rho-Kinase with High Kinase Selectivity and Antihypertensive Activity
- 15 December 2006
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 50 (1), 2-5
- https://doi.org/10.1021/jm060873p
Abstract
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.Keywords
This publication has 6 references indexed in Scilit:
- ROCKs as therapeutic targets in cardiovascular diseases.Expert Review of Cardiovascular Therapy, 2005
- Therapeutic Potential of Rho-Kinase Inhibitors in Cardiovascular DiseasesAmerican Journal of Cardiovascular Drugs, 2005
- ROCKs: multifunctional kinases in cell behaviourNature Reviews Molecular Cell Biology, 2003
- Copper-Catalyzed Coupling of Aryl Iodides with Aliphatic AlcoholsOrganic Letters, 2002
- Regulation and Functions of Rho-Associated KinaseExperimental Cell Research, 2000
- Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertensionNature, 1997