摘要
目的 合成含有替加氟的以卵磷脂类似物作载体的缀合物 ,并测定其生物活性。方法 将替加氟转化为羟烷基衍生物 ,六乙基亚磷酰三胺作磷酰化试剂 ,与羟烷基替加氟、1 十六烷基甘油及硫作用 ,经一锅法合成得到环甘油硫代磷脂羟烷基替加氟缀合物 ,通过三乙胺对环甘油硫代磷脂替加氟缀合物开环得到标题产物。结果 得到新化合物 9个 (2a～c ,3a～c ,4a～c) ,其结构经IR ,NMR和元素分析确证。结论 体外活性测定表明 ,化合物 4a对人体膀胱癌细胞的抑制效果比替加氟好。
AIM To synthesize the phosphocholine analogs containing tegafur and test their antitumor activity. METHODS N^1-(2-furanidyl)-5-fluorouracil reacted with multimethylene chlorohydrin in the presence of NaHCO_3 in acetonitrile at 80℃ to giveN^1-(2-furanidyl)-N^3-(hydroxyalkyl)-5-fluorouracil in high yield (≥93%). Its cyclic glycerothiophospholipid conjugate was synthesized by reaction of hexaethylphosphorous triamide, activated by a catalytic amount of iodine, as the phosphorylating reagent withN^1-(2-furanidyl)-N^3-(hydroxyalkyl)-5-fluorouracil and 1-O-hexadecyl glycerol as well as sulfur in a one-pot. Cyclic glycerothiophospholipid-nucleosides conjugate readily reacted with triethylamine to give the title compounds. RESULTS Nine new compounds (2a～c, 3a～c and 4a～c) have been synthesized. Their structures were confirmed by IR, ~1HNMR, ~ 13CNMR, ~ 31PNMR and elemental analysis. CONCLUSION The title compounds (4a～c) showed antitumor activity against human uriaryl bladder cancer cell and more effective than the tegafur.
出处
《药学学报》
CAS
CSCD
北大核心
2002年第11期858-862,共5页
Acta Pharmaceutica Sinica
基金
教育部高等学校重点实验室访问学者基金资助 .
