新型N-3位酰胺连噻唑烷-4-酮二芳基衍生物的设计合成及HIV逆转酶抑制活性

doi:10.6023/cjoc201509043

有机化学 ›› 2016, Vol. 36 ›› Issue (3): 527-532.DOI: 10.6023/cjoc201509043 上一篇下一篇

研究论文

新型N-3位酰胺连噻唑烷-4-酮二芳基衍生物的设计合成及HIV逆转酶抑制活性

陈华, 邵洁, 朱墨, 李小六

河北大学化学与环境科学学院河北省化学生物学重点实验室保定 071002

收稿日期:2015-09-30 修回日期:2015-12-02 发布日期:2015-12-07
通讯作者: 陈华, 李小六 E-mail:hua-todd@163.com;lixl@hbu.cn
基金资助:
国家自然科学基金(No. 21372060)、河北省自然科学杰出青年基金(培育)(No. B2015201005).

Design, Synthesis and Anti-HIV-Reverse Transcriptase Activity of Novel Diaryl Thiazolindin-4-one Derivatives Possessing Amide Linkage on N-3 Position

Chen Hua, Shao Jie, Zhu Mo, Li Xiaoliu

Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002

Received:2015-09-30 Revised:2015-12-02 Published:2015-12-07
Supported by:
Project supported by the National Natural Science Foundation of China (No. 21372060), the Hebei Province Natural Science Fund for Distinguished Young Scholars (Incubation) (No. B2015201005).

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1. 新型N-3位酰胺连噻唑烷-4-酮二芳基衍生物的设计合成及HIV逆转酶抑制活性.PDF(834KB)

摘要/Abstract

以氨基酸酯为原料, 在微波辐射条件下合成了系列N-3位含酯基的噻唑烷-4-酮衍生物, 经水解并酰胺缩合制备了N-3位酰胺键连接嘧啶胺的二芳基噻唑烷-4-酮衍生物. 化合物通过人类免疫缺陷病毒(HIV)逆转酶(RT)试剂盒(比色法)评价了其酶抑制活性. 活性结果表明, 部分化合物如5bb, 5bc, 5cb和5cc能有效地抑制HIV逆转酶的活性, IC₅₀值分别为4.15, 3.53, 4.61和4.06 μmol/L. 构效关系表明N-3位2个碳的柔性侧链以及亲脂基如甲基的引入将有利于化合物的抗HIV逆转录酶活性.

关键词: 噻唑烷-4-酮, 抗HIV逆转酶活性, 亲脂基团, 柔性侧链, 酰胺键

A series of thiazolidin-4-one derivatives possessing ester were synthesized under microwave irradiation using amino acid ester as starting material. After ester hydrolysis reaction and amide condensation reaction, the aimed diaryl thiazolindin-4-one derivatives possessing amide linkage on N-3 position were obtained. The compounds were evaluated for their human immunodeficiency virus (HIV-1) reverse transcriptase (RT) inhibitory activities in vitro HIV-1 RT kit assay (colorimetric method). The results showed that some of the compounds, such as 5bb, 5bc, 5cb, and 5cc could effectively inhibit RT activity with the IC₅₀ values of 4.15, 3.53, 4.61 and 4.06 μmol/L, respectively. Structure activity relationship analysis of these analogues suggested that the introduction of two carbons side chain on N-3 position and lipophilic group like methyl group should be favorable to their anti-HIV-RT activitives.

Key words: thiazolidin-4-one, anti-HIV-RT activity, lipophilic group, flexible side chain, amide bond

引用此文

陈华, 邵洁, 朱墨, 李小六. 新型N-3位酰胺连噻唑烷-4-酮二芳基衍生物的设计合成及HIV逆转酶抑制活性[J]. 有机化学, 2016, 36(3): 527-532.

Chen Hua, Shao Jie, Zhu Mo, Li Xiaoliu. Design, Synthesis and Anti-HIV-Reverse Transcriptase Activity of Novel Diaryl Thiazolindin-4-one Derivatives Possessing Amide Linkage on N-3 Position[J]. Chin. J. Org. Chem., 2016, 36(3): 527-532.

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新型N-3位酰胺连噻唑烷-4-酮二芳基衍生物的设计合成及HIV逆转酶抑制活性

Design, Synthesis and Anti-HIV-Reverse Transcriptase Activity of Novel Diaryl Thiazolindin-4-one Derivatives Possessing Amide Linkage on N-3 Position

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