1-烷基-5-氨基-6-苯乙基尿嘧啶的合成

1-烷基-5-氨基-6-苯乙基尿嘧啶的合成

马小艳, 程志坚, 陈艳丽, 李阿敏, 张志丽, 王孝伟, 刘俊义^*

1. 北京大学药学院化学生物学系, 北京 100191;
2. 北京大学天然药物及仿生药物国家重点实验室北京 100191;
3. 江西九江学院化学系, 江西九江 332005

收稿日期:2008-07-08 修回日期:2008-11-10 出版日期:2008-12-15 发布日期:2008-12-15
通讯作者: 刘俊义*

A convenient synthesis of 1-alkyl-5-amino-6-phenylethyluracils as potential non-nucleoside HIV-1RT inhibitors

Xiao-Yan Ma, Zhi-Jian Cheng, Yan-Li Chen, A-Min Li, Zhi-Li Zhang, Xiao-Wei Wang, Jun-Yi Liu^*

1. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China;
2.The State Key Laboratory of Nature and Biomimetic Drugs, Peking University, Beijing 100191, China;
3. Department of Chemistry, College of Jiujiang, Jiujiang 332005, China

Received:2008-07-08 Revised:2008-11-10 Online:2008-12-15 Published:2008-12-15
Contact: Jun-Yi Liu*

摘要/Abstract

摘要：

研究1-烷基-5-氨基-6-苯乙基尿嘧啶(1a, 1b)方便、高产率的合成方法, 此类化合物有可能作为非核苷类HIV-1RT抑制剂。以6-甲基尿嘧啶(2)为起始物, 经硝化、烷基化、苄基化及一锅反应脱苄基及还原反应等合成目标化合物, 并用NMR、MS、IR、Anal鉴定化合物结构。探索出了一种合成1-烷基-5氨基-6-苯乙基尿嘧啶类化合物的方便方法。首次于用3或4步反应、高产率合成了1-烷基-5-氨基-6-苯乙基尿嘧啶(1a, 1b)并发现化合物1a有中度抗HIV-1RT的活性 ( IC50 = 29 µM )。

关键词: HIV-1逆转录酶抑制剂, HIV-1逆转录酶抑制剂, HIV-1逆转录酶抑制剂, 1-烷基-5-氨基-6-苯乙基尿嘧啶, 1-烷基-5-氨基-6-苯乙基尿嘧啶, 1-烷基-5-氨基-6-苯乙基尿嘧啶, 尿嘧啶衍生物, 尿嘧啶衍生物, 尿嘧啶衍生物

Abstract:

1-Alkyl-5-amino-6-phenylethyluracils (1a, 1b) were synthesized as potential non-nucleoside HIV-1RT inhibitors. A convenient synthetic procedure was developed for the preparation of 1-alkyl-5-amino or 5-aminosubstituted-6-phenylethyluracils, which were synthesized in three or four steps from 6-methyluracil in good yield. The development of a one-pot reaction that simultaneously removed the benzyl protection group and reduced the nitro group greatly improved the yield of the synthesis. Compounds 1a and 1b are analogs of MKC-442, which is an efficient inhibitor of HIV-1 reverse transcriptase. 1a and 1b were tested for their inhibition of HIV-1RT, and moderate activity was found for 1a.

Key words: HIV-1 reverse transcriptase, HIV-1 reverse transcriptase, 1-Alkyl-5-amino-6-phenylethyluracils, 1-Alkyl-5-amino-6-phenylethyluracils, Uracil derivatives, Uracil derivatives, ,

Supporting: Foundation items: National Science Foundation of China (Grant No. 20672), the Doctoral grant of the Ministry of Education of China (Grant No. 2007000174).
^*Corresponding author. Tel.: 86-10-82801706

马小艳, 程志坚, 陈艳丽, 李阿敏, 张志丽, 王孝伟, 刘俊义^*
. 1-烷基-5-氨基-6-苯乙基尿嘧啶的合成[J]. .

Xiao-Yan Ma, Zhi-Jian Cheng, Yan-Li Chen, A-Min Li, Zhi-Li Zhang, Xiao-Wei Wang, Jun-Yi Liu^*
. A convenient synthesis of 1-alkyl-5-amino-6-phenylethyluracils as potential non-nucleoside HIV-1RT inhibitors
[J]. .