1427527-68-1Relevant articles and documents
Optimisation of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors
Ray, Peter,Wright, Jane,Adam, Julia,Boucharens, Sylviane,Black, Darcey,Brown, Angus R.,Epemolu, Ola,Fletcher, Dan,Huggett, Margaret,Jones, Phil,Laats, Steven,Lyons, Amanda,Man, Jos De,Morphy, Richard,Sherborne, Brad,Sherry, Lorcan,Straten, Nicole Van,Westwood, Paul,York, Mark
scheme or table, p. 1084 - 1088 (2011/04/16)
Rho kinase is an important target implicated in a variety of cardiovascular diseases. Herein, we report the optimisation of the fragment derived ATP-competitive ROCK inhibitors 1 and 2 into lead compound 14A. The initial goal of improving ROCK-I potency relative to 1, whilst maintaining a good PK profile, was achieved through removal of the aminoisoquinoline basic centre. Lead 14A was equipotent against both ROCK-I and ROCK-II, showed good in vivo efficacy in the spontaneous hypertensive rat model, and was further optimised to demonstrate the scope for improving selectivity over PKA versus hydroxy Fasudil 3.
