Design And Synthesis Of Dopamine Derivatives As Brain-targeted Drug For Antiparkinson

Objective: Parkionson’s disease(PD) is a progressiveneurodegenerative disorder which involves the loss of dopaminergicneurons of the substantia nigra pars compacta. In the clinical treatment ofPD, dopamine(DA) can’t be used directly to replenish the DA levels ofbrain, beacause it can’t migrate through the blood brain barrier and arriveat the central nervous system. At present, Levodopa(L-DOPA) has beenused as the main drugs for PD, However as the direct precursor of DA,most L-DOPA are decarboxylated by amino acid decarboxylase to DAthrough oral at the intestinal mucosa and peripheral tissue, which isresponsible for the gastrointestinal(nausea, emesis), and only a little ofL-DOPA can enter the central nervous system. It is believed that long-termuse of L-DOPA will lead to the appearance of dyskinesia, on-offphenomenon, intraday volatility phenomenon and other serious sideeffects. In order to overcome the shortcomings of L-DOPA, it is necessaryto design a more effective and safe drug as a substitute for L-DOPA in theclinical treatment of PD. Methods: Accordding to the physico-chemical property of DA andthe principles of prodrugs, a series of new piperazine of DA derivativesare designed and synthesized as potential drugs for PD treatment in thispaper.Results: The structures of these new compounds are identified by IR,MS and NMR, and further confirmed through the metabolic decompositionexperiment in vitro.Conclusion: The DA derivatives designed have been proved to bestable in blood and liver, and are promising to become the potentialbrain-targeted drugs.