Synthesis And Activity Studies Of Novel Cerebral Proective Anti-cereral Ischemic Drugs

Objective: Cerebrovascular disease is a kind of disease that affects the health andliving quality of human being seriously. Cerebral protective drugs can effectively relieve thesymptoms of cerebral ischemia and promote cell regeneration. Studies show that newCalcium Antagonist DY9836and Free Radical Scavenger Edaravone have good efficacies intreating cerebral ischemia. Free Radical Scavenger Edaravone has gone through clinicaltrials and been released to the market for many years. Edaravone also occupies a largemarket share. Therefore, the development of derivative products of DY9836and Edaravoneis of profound significance.Methods: In this paper, DY9836was synthesized through10-step reaction withCaffeic acid as the starting material. Then DY9836was modified by acylation or replacingthe functional groups of benzene ring of the piperazine, leading to seven target compoundswhich have not been reported. They all retained of ring-indazole and piperazine ring ofDY9836. Four edaravone derivative products were obtained by the condensation ofedaravone with benzaldehydes. And the structures of the11compounds were all comfirmedby¹H NMR,¹³C NMR and MS.Results: The overall yield of DY9836was10%, The purity of compounds are98%.The structure of compounds was confirmed by¹H-NMR and MS. In vitro nerve regenerationstudies showed that the nerve growth rates of six compounds are more than20percent. Invitro anti-DPPH radical activity test showed that only edaravone derivatives have radicalscavenging activity, the DY9836derivatives have no such biological activity. Furtherpharmacological testing is still ongoing.Conclusions: In the synthetic processes of these two series of compounds, the startingmaterials are cheap and easily obtained, the synthetic method is simple, the syntheticcompounds have high purity. So it has broad industrialization prospects. In vitro experimentsshowed that parts of DY9836and the edaravone derivatives have good biological activitieswhich have reference value for the further development and utilization of these compounds.