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Davis, Robert L.; Kahraman, Mehmet; Prins, Thomas J.; Beaver, Yan; Cook, Travis G.; Cramp, Jessica; Cayanan, Charmagne S.; Gardiner, Elisabeth M.M.; McLaughlin, Marsha A.; Clark, Abbot F.; Hellberg, Mark R.; Shiau, Andrew K.; Noble, Stewart A.; Borchardt, Allen J.
Bioorganic & medicinal chemistry letters, 06/2010, Letnik: 20, Številka: 11Journal Article
A benzothiophene containing Rho kinase inhibitor was identified in an ultra high-throughput enzymatic assay. SAR studies led to inhibitors with low nM enzymatic IC50s, low or sub-μM cellular EC50s in a novel label-free assay, and in vivo efficacy in a monkey model of ocular hypertension. 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.
