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

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Wu F, Buttner FH, Chen R, Hickey E, Jakes S, Kaplita P, Kashem MA, Kerr S, Kugler S, Paw Z, Prokopowicz A, Shih CK, Snow R, Young E, Cywin CL

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

Bioorg Med Chem Lett. 2010 Jun 1;20(11):3235-9. doi: 10.1016/j.bmcl.2010.04.070. Epub 2010 Apr 22.

PubMed ID

20462760 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Fasudil	Rho-associated protein kinase 1	IC 50 (nM)	660	N/A	N/A	Details