2-(1-取代哌啶-4-氨基)喹唑啉类化合物的合成及抗肿瘤活性研究(英文)  

Synthesis and antitumor activity of novel 2-(1-substitutedpiperidin-4-ylamino)quinazolines as antitumor agents

作　　者：王永康[1,2] 金晶[1] 朱丽娜[1] 张翼[1] 陈晓光[1] 高欣钦[2] 徐柏玲[1] 

机构地区：[1]中国医学科学院,北京协和医学院药物研究所,活性物质发现与适药化北京市重点实验室,北京100050 [2]大连理工大学精细化工国家重点实验室,辽宁大连116024

出　　处：《药学学报》2012年第9期1164-1178,共15页Acta Pharmaceutica Sinica

基　　金：Project supported by the National Natural Science Foundation of China(30500634);Natural Science Foundation of Beijing(7102112);"863"Program of China(2012AA020302)

摘　　要：本文合成了一系列新结构的2-(1-取代哌啶-4-氨基)喹唑啉衍生物,采用MTT法评价了化合物对5种肿瘤细胞系的抑制活性。研究结果表明:在哌啶环上引入小体积的疏水性烷基取代基,得到的化合物4j～4l、5a、5b和5d具有较强的细胞毒活性,IC50值在微摩尔水平。在小鼠移植瘤模型实验中,化合物4l表现出了较强的体内抗肿瘤活性,在200 mg.kg1的剂量下,对H22肿瘤生长抑制率为72.9%,对Lewis肺癌的抑制率达到了80%。A variety of novel 2-（1-substituted-piperidine-4-ylamino）quinazoline derivatives were prepared and their antiproliferative activities on five cancer cell lines were evaluated by MTT assay. Quinazolines 4j-41, 5a, 5b and 5d bearing a small hydrophobic alkyl group on piperidine ring exhibited potent antitumor activities with ICs0 values at micromolar level. Compound 41 displayed significant in vivo antitumor activity with 72.9% inhibition on H22 tumor growth and 80% inhibition on Lewis lung cancer growth at a dose of 200 mg kg-1.

关 键 词：喹唑啉 抗肿瘤剂 抗肿瘤活性 

分 类 号：R916[医药卫生—药学]