Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10594833 | Bioorganic & Medicinal Chemistry Letters | 2014 | 4 Pages |
Abstract
Rho-associated coiled coil-formed protein kinase (ROCK) inhibitors are under development as a new class of antiglaucoma agents. Based on the potent ROCK inhibitor H-1152, previously developed by us, we explored the possibility of related compounds as antiglaucoma agents and synthesized seven types of H-1152-inspired isoquinoline-5-sulfonamide compounds (H-0103-H-0107, H-1001, H-1005). Although all of these compounds potently inhibited ROCK (IC50Â =Â 18-48Â nM), only H-0104 and H-0106 exerted strong intraocular pressure (IOP)-lowering effects into the eyes of monkeys. These results suggested the possibility that there is no direct relationship between ROCK inhibition and IOP-lowering effects, indicating that the initial screening of compounds based on ROCK inhibitory activity may be an unsuitable strategy for developing antiglaucoma agents with potent IOP-lowering effects.
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Authors
Kengo Sumi, Yoshihiro Inoue, Masahiro Nishio, Yasuhito Naito, Takamitsu Hosoya, Masaaki Suzuki, Hiroyoshi Hidaka,