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

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Green J,Cao J,Bandarage UK,Gao H,Court J,Marhefka C,Jacobs M,Taslimi P,Newsome D,Nakayama T,Shah S,Rodems S

doi

10.1021/acs.jmedchem.5b00424

subject

Has Abstract

pub_date

2015-06-25 00:00:00

pages

5028-37

issue

12

eissn

0022-2623

issn

1520-4804

journal_volume

58

pub_type

杂志文章

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