Substituted 2H-isoquinolin-1-one as potent Rho-Kinase inhibitors. Part 1: Hit-to-lead account

Autor:	Steven Kerr, Charles L. Cywin, Frank H. Büttner, Frank Wu, Mohammed A. Kashem, Scott Jakes, Zofia Paw, Roger J. Snow, Erick R. R. Young, Eugene R. Hickey, Stanley Kugler, Paul Kaplita, Cheng-Kon Shih, Rhonda Chen, Anthony S. Prokopowicz
Rok vydání:	2010
Předmět:	Models Molecular Stereochemistry Clinical Biochemistry Pharmaceutical Science Blood Pressure Non-specific serine/threonine protein kinase Crystallography X-Ray Biochemistry In vivo Drug Discovery Animals Protein Kinase Inhibitors Molecular Biology Rho-associated protein kinase Antihypertensive Agents rho-Associated Kinases biology Drug discovery Chemistry Organic Chemistry Hit to lead Isoquinolines Rats Enzyme inhibitor biology.protein Molecular Medicine Signal transduction
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 20:3235-3239
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2010.04.070
Popis:	Two closely related scaffolds were identified through an uHTS campaign as desirable starting points for the development of Rho-Kinase (ROCK) inhibitors. Here, we describe our hit-to-lead evaluation process which culminated in the rapid discovery of potent leads such as 22 which successfully demonstrated an early in vivo proof of concept for anti-hypertensive activity.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c2d691a0169d6458e981f329be40c8b https://doi.org/10.1016/j.bmcl.2010.04.070 Zobrazit plný text záznamu Full Text from ScienceDirect