ROCK inhibitors 3: Design, synthesis and structure-activity relationships of 7-azaindole-based Rho kinase (ROCK) inhibitors

[Display omitted] •3-Substituted 7-azaindoles are shown to be bioisosteric replacements for 4-substituted pyridines.•Solubilizing groups are used to enhance solubility, potency and selectivity.•X-ray crystallography of target-ligand complexes provides clear illustration of selectivity. Rho kinase (ROCK) inhibitors are potential therapeutic agents for the treatment of a variety of disorders including hypertension, glaucoma and erectile dysfunction. Here we disclose a series of potent and selective ROCK inhibitors based on a substituted 7-azaindole scaffold. Substitution of the 3-position of 7-azaindole led to compounds such as 37, which possess excellent ROCK inhibitory potency and high selectivity against the closely related kinase PKA.