[Studies on synthesis and properties of N-benzoyl-THA targeting for brain]

It is the intent of these studies to synthesize acylated prodrugs of tacrine hydrochloride for improving the penetrating ability across the blood-brain barrier (BBB). Prodrugs of tacrine were prepared by benzoylation of the 9 amino group of THA. The structures of the synthesized prodrugs were determined by IR, 1H NMR, MS and UV. Their physical-chemical properties and stability under different conditions were investigated. The function of prodrugs targeting for brain were evaluated in vitro by biopartition micellar chromatography (BMC). The results showed that prodrugs were stable in different environments. Ethyl acetate/water partition coefficient indicated that the lipophilicity of prodrugs was increased, compared with THA. BMC predicted that prodrugs could improve the infiltration ability across BBB of parent-drug. It was suggested that this kind of prodrugs be a promising brain-targeting delivery system.