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一种新型Hsp90抑制剂的合成及其抑制活性 预览 被引量:1

Synthesis of Novel Hsp90 Inhibotor and Its Inhibition
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摘要 对氨基苯甲酸经重氮化后再与2-氯乙酰乙酸乙酯反应制得(Z)4-[2-(1-氯-2-乙氧基-2-羰亚甲基)肼基]苯甲酸(1);1与二甲基环己二酮成环后再与对羟基环己胺完成酰胺化反应合成了一种新型Hsp90抑制剂——N-(4-羟基环己基)-4-[1-(6,6-二甲基4-氧-3-乙酰氧基4,5,6,7-四氢吲唑)]苯甲酰胺(3),其结构经1H NMR表征。荧光偏振法研究结果表明3对Hsp90d具有明显的抑制活性。 (Z) -4- [ 2- ( 1 -chloro-2-ethoxy-2-oxoethylidene ) hydrazinyl ] benzoic acid ( 1 ) was prepared from p-aminobenzoic acid by diazotization, then reacted with ethyl 2-chloro-acetoacetate. A novel Hsp90 inhibotor, ethyl 1 - { 4- [ ( 4-hydroxycyclohexyl ) carbamoyl ] phenyl } -6,6-dimethyl-4-oxo-4,5,6, 7-tetrahydro-lH-indazole-3-carboxylate(3), was synthesized by cyclization between 1 and 5,5-dimethyl-cyclohexane-1,3-dione, then amidation with p-hydroxyl-cyclohexylamine. The structure was characterized by 1H NMR. The result from fluorescence polarization showed that 3 exhibited good inhibition against Hsp90α.
作者 张晓颖 张杰 李伟 王小龙 ZHANG Xiao-ying, ZHANG Jie, LI Wei, WANG Xiao-long ( Institute of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China)
出处 《合成化学》 CAS CSCD 北大核心 2011年第5期 659-661,共3页 Chinese Journal of Synthetic Chemistry
关键词 HSP90抑制剂 对氨基苯甲酸 环己二酮 荧光偏振法 抑制活性 合成 Hsp90 Inhibitor p-aminobenzoic acid cyclohexane-1,3-dione fluorescence polarization inhibition synthesis
作者简介 张晓颖(1986-),女,汉族,江苏连云港人,硕士研究生,主要从事合成药物的结构修饰及其构效关系的研究。E—mail:Scorpio_zxy@126.com 通信联系人:王小龙,博士,教授,Tel.025&6798015,E-mail:x.greg.wang@gmail.com
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