新型1,4-二苯并二氮杂酮类衍生物的合成及其抗癌活性

以取代邻硝基苯甲酸为起始原料，与二氯亚砜反应制得邻硝基苯甲酰氯，再与苯胺在碱性条件下反应制得酰胺衍生物(6a~6d);以醋酸钯为催化剂，6a~6d经NBS溴代制得溴代衍生物(7a~7d); 7a~7d依次经N-烷基化反应，还原反应和分子内C-N键环合反应合成了10个新型的1,4-二苯并二氮杂酮类化合物(10a~10j),产率61%~78%，其结构经¹H NMR, ¹³C NMR和HR-MS(ESI)表征。初步体外活性测试结果表明:10a~10j对非小细胞肺癌细胞（A549）,人乳腺癌细胞（MDA-MB-231）和宫颈癌细胞(HeLa)均有抑制作用。其中,10g和10i对A549, 10g对MDA-MB-231, 10h和10i对HeLa的抑制率大于50%。

Synthesis of Novel 1,4-Dibenzodiazepin Compounds and Their Anticancer Activities

The amide derivatives(6a~6d) were obtained by the reaction of substituted o-nitrobenzoic acids with SOCl2, then reaction with aniline under basic condition.The brominated derivatives(7a~7d) were prepared by NBS-bromination of 6a~6d, using Pd(OAc)2 as the catalyst.Ten novel 1,4-dibenzodiazepin compounds(10a~10j) were synthesized by the reaction of N-alkylation, reduction and intramolecular C-N bond cyclization from 7a~7d, respectively.The structures were characterized by 1H NMR, 13C NMR and HR-MS(ESI).The preliminary in vitro bio-activity tests showed that 10a~10j had certain inhibitory effects on non-small cell lung cancer cell(A549), human breast cancer cell(MDA-MB-231) and cervical cancer cell(HeLa).Among them, the inhibition rates of 10g and 10i on A549, 10g and 10h on MDA-MB-231 and 10i on HeLa were above 50%.