Design and synthesis of Rho kinase inhibitors (I)

Structure-based design of several scaffolds of Rho kinase inhibitor was performed by using pharmacophore information obtained from a high-throughput screening and the enzyme homology model. Several structurally unrelated scaffolds of the Rho kinase inhibitor were designed using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. A docking simulation using the ligand-binding pocket of the Rho kinase model helped to comprehensively understand and to predict the structure–activity relationship of the inhibitors. This understanding was useful for developing new Rho kinase inhibitors of higher potency and selectivity. We identified several potent platforms for developing the Rho kinase inhibitors, namely, pyridine, 1 H-indazole, isoquinoline, and phthalimide.