3,4-取代喹啉酮类衍生物的合成及其对HIV-1逆转录酶的抑制活性  

Synthesis and HIV-1 reverse transcriptase inhibitory activity of 3,4-substituted quinolinone derivatives

作　　者：黎文海[1] 侯金明[1] 尤启冬[2] 

机构地区：[1]中国药科大学物理化学教研室,江苏南京211198 [2]中国药科大学药物化学教研室,江苏南京210009

出　　处：《中国药物化学杂志》2009年第1期20-26,共7页Chinese Journal of Medicinal Chemistry

摘　　要：目的设计合成新型喹啉酮类化合物并研究其对HIV-1逆转录酶的抑制活性。方法以丙二酸二乙酯为原料,经烷基化反应得2-取代丙二酸二乙酯,它再与对氯苯胺或3,4-二氟苯胺缩合,用多聚磷酸环合,最后与卤代烃、取代苯甲酰氯反应得到目标化合物;并对目标化合物进行了初步的体外HIV-1逆转录酶抑制活性筛选。结果与结论合成了24个新化合物,其结构经IR、1H-NMR、MS谱及元素分析确证。初步的药理试验表明,24个目标化合物中有6个化合物具有一定的HIV-1逆转录酶抑制活性。Aim To find new compounds with potent HIV-1 RT inhibitory activity for the prevention and treatment of human immunodeficiency virus. Methods Firstly, alkylation of diethyl malonate gave 2-subst/tuted diethyl malonate （2）. Secondly, compound 2 was condensed with p-chloroaniline or 3,4-fluoride aniline, then cyclization with PPA to give compound 4. Finally, compound 4 was reacted with halohydrocarbon, substituted benzoyl chloride to give the target compounds. Results and conclusion Twenty-four target compounds of modified quinolinones were synthesized and their structures were confLrrned by IR, MS, ^1H-NMR and element analysis. The results of preliminary pharmacological test show that six of twenty-four compounds possess diverse HIV-1 RT inhibitory activity.

关 键 词：3 4-取代喹啉酮 HIV-1逆转录酶抑制剂 合成 抑制活性 

分 类 号：R914[医药卫生—药物化学]