Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369550 | Bioorganic & Medicinal Chemistry Letters | 2014 | 5 Pages |
Abstract
A series of 2,3,6-pyrazine Rho Kinase inhibitors were optimized for in vivo activity for topical ocular dosing. Modifications of the 2-(piperazin-1-yl)pyrazine derivatives produced compounds with improved solubility and physicochemical properties. Modifications of the 6-pyrazine substituent led to improvements in in vitro potency. Compound 9 had the best in vitro and in vivo potency of EC50 = 260 nM with a 30% reduction of IOP in a non-human primate model at a dose of 0.33%.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Hwang-Hsing Chen, Abdelmoulah Namil, Bryon Severns, Jennifer Ward, Curtis Kelly, Colene Drace, Marsha A. McLaughlin, Shenouda Yacoub, Byron Li, Raj Patil, Naj Sharif, Mark R. Hellberg, Andrew Rusinko, Iok-Hou Pang, Keith D. Combrink,