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

Abstract A new series of ( Z )‐2‐(4‐(7 H ‐pyrrolo[2,3‐ d ]pyrimidin‐4‐yl)piperazin‐1‐yl)‐5‐(benzylidene)‐1,5‐dihydro‐4 H ‐imidazol‐4‐ones ( 5a−t ) has been synthesized via a seven‐step pathway with various substituted benzaldehydes yielding various derivatives as ROCK inhibitors. 1 H NMR, 13 C 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.