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  • Design, Synthesis, and Structure-Activity Relationships of Pyridine-Based Rho Kinase (ROCK) Inhibitors.

Design, Synthesis, and Structure-Activity Relationships of Pyridine-Based Rho Kinase (ROCK) Inhibitors.

Journal of medicinal chemistry (2015-06-04)
Jeremy Green, Jingrong Cao, Upul K Bandarage, Huai Gao, John Court, Craig Marhefka, Marc Jacobs, Paul Taslimi, David Newsome, Tomoko Nakayama, Sundeep Shah, Steve Rodems
要旨

The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction. Beginning with compound 4, an inhibitor of ROCK1 identified through high-throughput screening, systematic exploration of SAR, and application of structure-based design, led to potent and selective ROCK inhibitors. Compound 37 represents significant improvements in inhibition potency, kinase selectivity, and CYP inhibition and possesses pharmacokinetics suitable for in vivo experimentation.

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Millipore
Multiscreen®96ウェルプレート、ポリカーボネートメンブレン, pore size 5.0 μm, sterile