Benzothiophene containing Rho kinase inhibitors: Efficacy in an animal model of glaucoma.
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.
Davis
Robert L
RL
Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA. rdavis@kalypsys.com
Kahraman
Mehmet
M
Prins
Thomas J
TJ
Beaver
Yan
Y
Cook
Travis G
TG
Cramp
Jessica
J
Cayanan
Charmagne S
CS
Gardiner
Elisabeth M M
EM
McLaughlin
Marsha A
MA
Clark
Abbot F
AF
Hellberg
Mark R
MR
Shiau
Andrew K
AK
Noble
Stewart A
SA
Borchardt
Allen J
AJ
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*
D047428:Protein Kinase Inhibitors; D013876:Thiophenes; C088015:benzothiophene; D054460:rho-Associated Kinases