title: Benzothiophene containing Rho kinase inhibitors: Efficacy in an animal model of glaucoma.
abstract: We identified a new benzothiophene containing Rho kinase inhibitor scaffold in an ultra high-throughput enzymatic activity screen. SAR studies, driven by a novel label-free cellular impedance assay, were used to derive 39, which substantially reduced intraocular pressure in a monkey model of glaucoma-associated ocular hypertension.
authors.affiliation: Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA. rdavis@kalypsys.com
authors.forename: Robert L
authors.initials: RL
authors.lastname: Davis
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kahraman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Prins
authors.forename: Yan
authors.initials: Y
authors.lastname: Beaver
authors.forename: Travis G
authors.initials: TG
authors.lastname: Cook
authors.forename: Jessica
authors.initials: J
authors.lastname: Cramp
authors.forename: Charmagne S
authors.initials: CS
authors.lastname: Cayanan
authors.forename: Elisabeth M M
authors.initials: EM
authors.lastname: Gardiner
authors.forename: Marsha A
authors.initials: MA
authors.lastname: McLaughlin
authors.forename: Abbot F
authors.initials: AF
authors.lastname: Clark
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hellberg
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Shiau
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Noble
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Borchardt
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005901:Glaucoma / Q000201:enzymology* / Q000503:physiopathology; D000882:Haplorhini; D006367:HeLa Cells; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D009798:Ocular Hypertension / Q000201:enzymology* / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D013876:Thiophenes; C088015:benzothiophene; D054460:rho-Associated Kinases