N^8-去氮-N^5-取代四氢叶酸类似物的设计合成及生物活性研究  

Studies on Synthesis and Bioactivity of N^8-Deaza-N^5-tetrahydrofolate Analogues

作　　者：闫汝锋[1] 田超[1] 郭莹[1] 张志丽[1] 王孝伟[1] 刘俊义[1] 

机构地区：[1]北京大学药学院化学生物学系,北京100191

出　　处：《有机化学》2010年第11期1721-1725,共5页Chinese Journal of Organic Chemistry

摘　　要：以2,4-二氨基-6-羟甲基吡啶并[3,2-d]嘧啶为原料,在4-位氨基转换为羟基后与对氨基苯甲酰谷氨酸二乙酯连接生成叶酸类似物分子骨架,采用Adams催化方法还原吡啶环,在N5-位连接不同类型的取代基得到3个新的N8-去氮四氢叶酸类似物.经1H NMR,MS对化合物的结构进行了表征.初步生物活性结果表明,此类化合物对人重组二氢叶酸还原酶的抑制活性与N5-位的取代基有关联.The backbone of folate analogue was obtained by linking diethyl-N-（p-aminobenzoyl）-Lglutamate and 2-amino-4-hydroxy-6-（hydroxymethyl）pyridopyrimidine.Three new 8-deazatetrahydrofolate analogues were synthesized after reducing the pyrimidine and linking different substituents on N^5 position.The compounds were characterized by 1H NMR and MS techniques.The inhibitory activities of the compounds against human dihydrofolate reductase were determined.The results showed that the bioac-tivities of the compounds were related with different substituents on N^5 position.

关 键 词：N^8-去氮-N^5-取代叶酸类似物 二氢叶酸还原酶 抗癌 

分 类 号：O6213[理学—有机化学]