含1,3,4-噻二唑的5-氟尿嘧啶衍生物的合成及其抗肿瘤活性  

Synthesis of novel 5-fluorouracil derivatives containing 1,3,4-thiadiazole and their antitumor activities

作　　者：郑开波[1] 何俊[1] 张杰[2] 

机构地区：[1]四川大学化学学院,四川成都610064 [2]四川大学华西医院,四川成都610041

出　　处：《华西药学杂志》2008年第5期528-530,共3页West China Journal of Pharmaceutical Sciences

摘　　要：目的制备低毒、高抗瘤活性的N1-乙酰氨基-(5-烃基/芳基-1,3,4-噻二唑-2-基)-5-氟尿嘧啶衍生物。方法以5-氟尿嘧啶为原料,在氢氧化钾的作用下与氯乙酸反应后,与合成的中间体2-氨基-5-取代-1,3,4-噻二唑反应制得目标物,并评价其抗肿瘤活性。结果和结论合成了7个未见文献报道的目标物3 a^3 g,并用1HNMR、HRMS、IR确认了结构;目标化合物3 d、3 f和3 g有较好的抗肿瘤活性。OBJECTIVE To synthesize N1 - acetylamino - （ 5 - alkyl/aryl - 1,3,4 - thia - diazole - 2 - yl ） - 5 - fluorouracil derivatives which has less toxicities and higher antitumor activities. METHODS The target compounds were sythesized from the reactions of 5 - fluorouracil and chloroacetic acid in the existence of potassium hydroxide, then coupled with 2 - amino - 5 - alkyl/aryl - 1, 3,4 - thiadiazole. Their bioactivities were evaluated. RESULTS and CONCLUSION Seven novel target compounds 3 a - 3 g were synthesized which had been confirmed by IR, 1HNMR and HRMS. 3 d ,3 f and 3 g could strongly inhibit the proliferation of tumor cells in vitro.

关 键 词：5-氟尿嘧啶衍生物 1 3 4-噻二唑 合成 抗肿瘤 

分 类 号：R914[医药卫生—药物化学]