Benzothiophene containing Rho kinase inhibitors: Efficacy in an animal model of glaucoma

Robert L Davis; Mehmet Kahraman; Thomas J Prins; Yan Beaver; Travis G Cook; Jessica Cramp; Charmagne S Cayanan; Elisabeth M M Gardiner; Marsha A McLaughlin; Abbot F Clark; Mark R Hellberg; Andrew K Shiau; Stewart A Noble; Allen J Borchardt

doi:10.1016/j.bmcl.2010.04.020

Benzothiophene containing Rho kinase inhibitors: Efficacy in an animal model of glaucoma

Bioorg Med Chem Lett. 2010 Jun 1;20(11):3361-6. doi: 10.1016/j.bmcl.2010.04.020. Epub 2010 Apr 11.

Authors

Robert L Davis¹, Mehmet Kahraman, Thomas J Prins, Yan Beaver, Travis G Cook, Jessica Cramp, Charmagne S Cayanan, Elisabeth M M Gardiner, Marsha A McLaughlin, Abbot F Clark, Mark R Hellberg, Andrew K Shiau, Stewart A Noble, Allen J Borchardt

Affiliation

¹ Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA. rdavis@kalypsys.com

PMID: 20434334
DOI: 10.1016/j.bmcl.2010.04.020

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.

MeSH terms

Animals
Disease Models, Animal*
Glaucoma / enzymology*
Glaucoma / physiopathology
Haplorhini
HeLa Cells
Humans
Intraocular Pressure / drug effects
Ocular Hypertension / enzymology*
Ocular Hypertension / physiopathology
Protein Kinase Inhibitors / pharmacology*
Thiophenes / pharmacology*
rho-Associated Kinases / antagonists & inhibitors*

Substances

Protein Kinase Inhibitors
Thiophenes
benzothiophene
rho-Associated Kinases