HIV-1 逆转录酶抑制剂的合成及活性评价

doi:10.5246/jcps.2011.02.018

HIV-1 逆转录酶抑制剂的合成及活性评价

闫寒, 王孝伟^*, 郭盈, 张志丽, 刘俊义^*

1. 北京大学医学部药学院化学生物学系, 北京 100191
2. 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

收稿日期:2010-11-29 修回日期:2011-02-10 出版日期:2011-03-15 发布日期:2011-03-15
通讯作者: 王孝伟*,刘俊义*

Synthesis and anti-HIV-1 activity evaluation of N-1-alkyl-5-halogeno-6-alkylamino uracils as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

Han Yan, Xiao-Wei Wang^*, Ying Guo, Zhi-Li Zhang, Jun-Yi Liu^*

1. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. State key Laboratory of Natural and Biomimetic Drug, Peking University Health Science Center, Beijing 100191 China

Received:2010-11-29 Revised:2011-02-10 Online:2011-03-15 Published:2011-03-15
Contact: Xiao-Wei Wang*, Jun-Yi Liu*

摘要/Abstract

摘要：

本研究以HIV-1逆转录酶为靶点, 设计了一类具有HEPT类结构的化合物: 1-乙氧基甲基/苄氧基甲基-5-卤代-6-脂肪胺尿嘧啶作为抑制剂, 并对合成的目标化合物进行了生物活性测定, 一些化合物显示出较强的抗HIV生物活性, 与对照物奈韦拉平相比(IC50 8.30 µM) 化合物1d, 1m 和1n 的IC50值分别达到了13.3, 11.7和3.15 µM。

关键词: HIV-1逆转录酶, 非核苷类逆转录酶抑制剂, HEPT类似物

Abstract: N-1-alkyl-5-halogeno-6-alkylamino uracils, which are novel 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio) thymine (HEPT) analogues, were synthesized as the selective and potent non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitors. Some of the compounds showed potent inhibitory activity against HIV-1 reverse transcriptase. For instance, compounds 1d, 1m and 1n exhibited potent anti-HIV-1 activity with the IC50 values of 13.3, 11.7 and 3.15 µM, respectively, which are comparable to that of nevirapine (IC50 8.38 µM).

Key words: HIV-1 reverse transcriptase, Non-nucleoside reverse transcriptase inhibitors, HEPT analogues

中图分类号:

R916

Supporting:

Foundation items: National Natural Science Foundation of China (Grant No. 20672008 and 20972011).
^*Corresponding author. Tel.: 86-10-82801706

闫寒, 王孝伟^*, 郭盈, 张志丽, 刘俊义^*. HIV-1 逆转录酶抑制剂的合成及活性评价[J]. , DOI: 10.5246/jcps.2011.02.018.

Han Yan, Xiao-Wei Wang^*, Ying Guo, Zhi-Li Zhang, Jun-Yi Liu^* . Synthesis and anti-HIV-1 activity evaluation of N-1-alkyl-5-halogeno-6-alkylamino uracils as novel non-nucleoside HIV-1 reverse transcriptase inhibitors [J]. , DOI: 10.5246/jcps.2011.02.018.

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