L-鸟苷类似物前药: 设计、合成与抗HIV活性

doi:10.5246/jcps.2011.04.041

L-鸟苷类似物前药: 设计、合成与抗HIV活性

卢俊峰, 谢璐佳, 曹眸, 关注^*, 郭颖, 杨振军^*, 张礼和

1. 北京大学医学部天然药物及仿生药物国家重点实验室, 北京 100191
2. 中国医学科学院中国协和医科大学药物研究所, 北京 100050

收稿日期:2011-01-12 修回日期:2011-04-20 出版日期:2011-07-01 发布日期:2011-07-01
通讯作者: 关注*, 杨振军*

The prodrugs of L-guanosine analogs: design, synthesis and anti-HIV activity

Jun-Feng Lu, Lu-Jia Xie, Mou Cao, Zhu Guan^*, Ying Guo, Zhen-Jun Yang^*, Li-He Zhang

1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Institute of Meteria Medica, Chinese Academy of Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

Received:2011-01-12 Revised:2011-04-20 Online:2011-07-01 Published:2011-07-01
Contact: Zhu Guan*, Zhen-Jun Yang*

摘要/Abstract

摘要： 为了提高鸟嘌呤核苷类似物的药代动力学和稳定性, 设计合成了取代氨基修饰L-ddG和L-D4G的6位, 得到一系列的前药, 经NMR、MS、高分辨质谱确定了化合物结构, 发现化合物7d 和 8g有中等抗HIV的活性 (EC50 = 42, 55 μmol/L)。

关键词: L-2',3'-二脱氧-鸟嘌呤核苷, L-2',3'-二羟基-2',3'-二脱氧-鸟嘌呤核苷, 前药, 抗HIV

Abstract: To improve the stability and pharmacokinetic properties, prodrugs of L-ddG (L-2',3'-dideoxy-guanosine) and L-D4G (L-2',3'-dihydro-2',3'-dideoxyguanosine) modified with a series of substituted amino groups at C-6 position of the purine base were designed and synthesized and their anti-HIV activities were evaluated. Compounds 7d and 8g exhibited moderate activity and showed EC50 of 42 μmol/L and 55 μmol/L, respectively.

Key words: L-ddG, L-D4G, Prodrug, Anti-HIV

中图分类号:

R916

Supporting:

Foundation items: National Natural Science Foundation of China (Grant No. 20472006 and 20832001).
^*Corresponding author. Tel./Fax: 86-10-82802503;
E-mail: yangzj@bjmu.edu.cn; guanzhu_gz@bjmu.edu.cn

卢俊峰, 谢璐佳, 曹眸, 关注^*, 郭颖, 杨振军^*, 张礼和. L-鸟苷类似物前药: 设计、合成与抗HIV活性[J]. , DOI: 10.5246/jcps.2011.04.041.

Jun-Feng Lu, Lu-Jia Xie, Mou Cao, Zhu Guan^*, Ying Guo, Zhen-Jun Yang^*, Li-He Zhang. The prodrugs of L-guanosine analogs: design, synthesis and anti-HIV activity [J]. , DOI: 10.5246/jcps.2011.04.041.

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