Design And Synthesis Of Edaravone's Water-soluble Derivatives

Edaravone ,of which trade name is BICUN and chemical name is 3-methyl-1-phenyl-2-pyrazolin-5-one is a new brain protective agent. It keeps brain cells , vascular endothelial cells , nerve cells from oxidative damage by scavenging free radicals and inhibiting lipid peroxidation. In clinical it is mainly used to improve the neurological symptoms caused by acute cerebral infarction and activities of daily life and dysfunction ;besides, it is used for the treatment of subarachnoid hemorrhage at acute stage. Because edaravone is insoluble in water and susceptible to oxidation, the preparation often need to be added basic substances and antioxidants which may cause unnecessary side effect to patients to increase its water solubility and stability. Accordding to the physico-chemical property of edaravone and the principles of prodrugs, a series of new amino carbonic and ester of edaravone derivatives are designed and synthesized in this paper. The structures of these new compounds are also confirmed. After experiments on physico-chemical property and pharmacodynamic action of these new compounds , they are concluded that these new compounds have satisfactory water-solubility and stability and show the same brain protective action as edaravone on rats; besides, these new compounds are effective oral or injected.