新型1,4-苯并二氮杂-5-酮三氟乙基和环丙基取代衍生物的合成及抗肿瘤活性初探  

Synthesis and Antitumor Activities of 1,4-Benzodiazepine-5-ones Trifluoroethyl and Cyclopropyl Substituted Derivatives

作　　者：李斌 何菱[1] LI Bin;HE Ling(West China School of Pharmacy,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《合成化学》2022年第8期597-602,共6页Chinese Journal of Synthetic Chemistry

基　　金：川大-泸州战略合作项目(2017CDLZ-S34)。

摘　　要：以邻硝基苯甲酸衍生物为底物,经3或4步反应,并在第3步关环反应中使用了乙酰丙酮钼和三氟甲磺酸铜作为催化剂,合成了10个新型的1,4-苯并二氮杂-5-酮三氟乙基和环丙基取代衍生物(4a~4f,5a~5b,6a~6b),其结构经^(1)H NMR,^(13)C NMR和HR-MS(ESI)表征。测试了目标化合物对慢性骨髓性白血病细胞、乳腺癌、肺癌和宫颈癌等4种肿瘤细胞系的抑制活性。结果表明:化合物2-(丙-1-烯-2-基)-4-(2,2,2-三氟乙基)-1,2,3,4-四氢-5 H-苯并[e][1,4]二氮杂-5-酮(4a)对慢性骨髓性白血病细胞K562的IC_(50)可达2.6μM;目标化合物对肺癌A549、乳腺癌MDA-MB-231和宫颈癌HeLa细胞系也表现出一定的抑制活性。Using o-nitrobenzoic acid derivatives as substrates,the reaction was carried out in 3~4 steps,with molybdenum acetylacetonate and copper trifluoromethanesulfonate acting as catalysts in the third step,ten novel 1-benzodiazo-5-one trifluoroethyl and cyclopropyl substituted derivatives were synthesized and their structures were characterized by ^(1)H NMR,^(13)C NMR and HR-MS(ESI).The tumor inhibitory activity of breast cancer,lung cancer,cervical cancer and chronic myelogenous leukemia cells lines were tested.Among them,the IC_(50) value of 2-(prop-1-en-2-yl)-4-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydro-5 H-benzo[e][1,4]diazepin-5-one(4a)against chronic myelogenous leukemia cells lines K562 can reach 2.6μM.At the same time,the target compounds also showed certain inhibitory activity on breast cancer MDA-MB-231,lung cancer A549 and cervical cancer HeLa cell lines.

关 键 词：苯并二氮杂 三氟乙基 环丙基 抗肿瘤活性 过渡金属催化合成 臭氧氧化 

分 类 号：O621.3[理学—有机化学]