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

作　　者：陈华[1] 邵洁[1] 朱墨[1] 李小六[1] 

机构地区：[1]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

出　　处：《有机化学》2016年第3期527-532,共6页Chinese Journal of Organic Chemistry

基　　金：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)~~

摘　　要：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,IC_(50)值分别为4.15,3.53,4.61和4.06μmol/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.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.

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 

分 类 号：O626[理学—有机化学]