Synthesis, Docking and Rho Kinase Inhibition of Novel Piperazine-7-Deazapurine Based Imidazolidone Derivatives

A new series of (Z)-2-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl)-5-(benzylidene)-1,5-dihydro-4H-imidazol-4-ones (5a-t) has been synthesized via a seven-step pathway with various substituted benzaldehydes yielding various derivatives as ROCK inhibitors. H-1 NMR, C-13 NMR, and HRMS spectral analysis were used to describe all the novel target compounds. We examined the effects of various aromatic substitutions on the inhibition of ROCK-I & ROCK-II using molecular modeling analysis. Although molecular docking revealed a range of binding affinities, a majority of the synthesized compounds demonstrated low inhibitory activities (pIC(50) < 6.0), with no significant improvement over CCT129254 (4). This investigation highlights the complexities in developing potent and selective ROCK inhibitors and lays the groundwork for future enhancements in cancer therapeutics.