Cardiovascular effects of a novel potent and highly selective azaindole-based inhibitor of Rho-kinase.

ABSTRACT:

Background and purpose

Rho-kinase (ROCK) has been implicated in the pathophysiology of altered vasoregulation leading to hypertension. Here we describe the pharmacological characterization of a potent, highly selective and orally active ROCK inhibitor, the derivative of a class of azaindoles, azaindole 1 (6-chloro-N4-{3,5-difluoro-4-[(3-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-phenyl}pyrimidine-2,4-diamine).

Experimental approach

Pharmacological characterization of azaindole 1 was performed with human recombinant ROCK in vitro. Vasodilator activity was determined using isolated vessels in vitro and different animal models in vivo.

Key results

This compound inhibited the ROCK-1 and ROCK-2 isoenzymes with IC50 s of 0.6 and 1.1 nM in an ATP-competitive manner. Although

SUBMITTER: Kast R 

PROVIDER: S-EPMC2095102 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature