O-(1-芳硒基-3-叠氮基)异丙基- O-2-(N3-替加氟)烷基硫代磷酯的合成与活性

以碘作催化剂, 无水苯为溶剂, 六乙基亚磷酰三胺依次与羟乙基替加氟、1-芳硒基甘油及硫反应, 得中间体硒代环甘油磷脂替加氟缀合物2a～2f. 以无水N,N-二甲基甲酰胺(DMF)作溶剂, 室温下, 叠氮化钠中对2a～2f进行亲核开环, 得到O-(1-芳硒基-3-叠氮基)异丙基-O-2-(N3-替加氟)乙基硫代磷酯. 体外活性测试结果表明, 目标化合物3a～3f 对膀胱癌细胞PGA1抑制作用比替加氟高, 对胃癌细胞BGC-823的抑制作用与替加氟相当.

Synthesis and Antitumor of O-(1-Arylseleno-3-azido)isopropyl-O-2-(N~3-tegafur)alkyl Thiophosphate

The intermediates 2a～2f of cyclic (l-arylseleno)glycerol phosphate and tegafur conjugates were synthesized by one-pot reaction of hexaethyl phosphorous triamide, activated by a catalytic amount of iodine, with (N~3-tegafur)alkanol, 1-arylselenoglycerol and sulphur successively in refluxing benzene. O-(1-Arylseleno-3-azido)isopropyl-O-2-(N~3-tegarur)alkyl thiophosphate (3a～3f) were obtained via nu-cleophilic ring-opening of sodium azide to 2a～2f in dry DMF at room temperature, and their antitumor activities were tested. The results showed that their antimutor activities were higher than tegafur against human urinary bladder cancer cell PGA_1, and equivalent to tegafur against BGC-823.