| 5-Fluorouracil (5-FU), first synthesized in 1957, is one of theantitumor agents frequently used for treating solid tumors. However, theclinical applications of 5-FU are subjected to great limitations because ofits short plasma half-life,poorly tumor selectivity,intestinal toxicity andso on. To tackle these problems, numerous modifications of the 5-FUstructure have been performed to develop new prodrugs of 5-FU as leadcompounds with high efficiency and low toxicity．On the basis of the predecessors research, we used ester bond aslinkage, designed and synthesized three types of 5-Fluorouracil esterderivatives, at the same time, we also used other bond as linkagesynthesized kinds of compounds containing fluorouracil to analysis therelationship between structure and activities. The first is aryl of 5-FUester derivatives, four compounds of this kind were also sythesised withthe linkage of C-N for comparison; The second is six novel 5-fluorouracil erster and amide bond; The third category is tert-butyl 5-fluorouracil esterderivatives.Their structures were confirmed through IR, 1H NMR, 13C NMR,MS and elemental analysis. The properties of thermal behavior of thesecompounds were systematically investigated, and their octanol-waterpartition coefficients (lg P) were calculated by HPLC. The in vitroantitumor activity test showed that these compounds have certainantitumor activities to HL-60 and BEL-7402 cells, and the ester bond of5-fluorouracil derivatives has a better inhibitory rate than the otherlinkages.
|
PDF Full Text Request