Benzimidazole- and benzoxazole-based inhibitors of Rho kinase.
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.
Sessions
E Hampton
EH
Department of Molecular Therapeutics, The Scripps Research Institute Florida, 130 Scripps Way, #2A1, Jupiter, FL 33458, USA.
Yin
Yan
Y
Bannister
Thomas D
TD
Weiser
Amiee
A
Griffin
Evelyn
E
Pocas
Jennifer
J
Cameron
Michael D
MD
Ruiz
Claudia
C
Lin
Li
L
Schürer
Stephan C
SC
Schröter
Thomas
T
LoGrasso
Philip
P
Feng
Yangbo
Y
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
D001562:Benzimidazoles; D001583:Benzoxazoles; D002839:Chromans; D011720:Pyrazoles; D011743:Pyrimidines; D054460:rho-Associated Kinases