Synthesis And Antitumor Activities Of 5-Fluorouracil Derivatives Containing Phosphorus

5-Fluorouracil and Tegafur[l-(tetrahydrofiiran-2-yl)-5-fluorouracil] are both antitumor drugs which are widely used in clinic. However, their bad selectivitity and evident side effects limit their application. In recent years, many chemists have modified their chemical structures and hope to develop a better drug to overcome its shortcomings.In order to search novel 5-fluorouracil derivative antitumor drugs, we designed and synthesized 20 novel tegafur containing phosphorus compounds. Their structures were confirmed by IR, 1H NMR, 31P NMR, MS and elemental analysis. The properties of physical, chemical and spectroscopy of these compounds were systematically investigated. The reaction methods and reaction conditions were also investigated. The molecular formulas of the title compounds can be shown asfollows respectively.( I )1 -(tetrahydrofuran-2-yl)-3-[4-(O,O-dialkylthiophosphoryl,S-methylenecarbony-loxo)alkyl]-5-fluorouraciln=4, R=Me , Et, n-Pr, i-Pr, n-Bu , i-Bu. n=2, R=Et (II)1 -(tetrahydrofuran-2-yl)-3-(O,O-dialkylphosphono-alkoxylcarbonylmethylene)-5-fluorouracilThe results of preliminary bioassay show that the new compounds possess some extent of antitumor activities. Moreover, the second type of compounds exhibit good fungicidal activities. At the same time, it also provided basic experimental date about structure-activity relationship of these two kinds of compounds.