title: Benzimidazole- and benzoxazole-based inhibitors of Rho kinase.
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.
authors.affiliation: Department of Molecular Therapeutics, The Scripps Research Institute Florida, 130 Scripps Way, #2A1, Jupiter, FL 33458, USA.
authors.forename: E Hampton
authors.initials: EH
authors.lastname: Sessions
authors.forename: Yan
authors.initials: Y
authors.lastname: Yin
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bannister
authors.forename: Amiee
authors.initials: A
authors.lastname: Weiser
authors.forename: Evelyn
authors.initials: E
authors.lastname: Griffin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pocas
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cameron
authors.forename: Claudia
authors.initials: C
authors.lastname: Ruiz
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Schürer
authors.forename: Thomas
authors.initials: T
authors.lastname: Schröter
authors.forename: Philip
authors.initials: P
authors.lastname: LoGrasso
authors.forename: Yangbo
authors.initials: Y
authors.lastname: Feng
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D001583:Benzoxazoles / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002839:Chromans / Q000737:chemistry; D015195:Drug Design; D005901:Glaucoma / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D008861:Microsomes / Q000187:drug effects; D008862:Microsomes, Liver / Q000378:metabolism; D008956:Models, Chemical; D011720:Pyrazoles / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D001583:Benzoxazoles; D002839:Chromans; D011720:Pyrazoles; D011743:Pyrimidines; D054460:rho-Associated Kinases