含1,2,4-三唑环的亚胺及酰亚胺类化合物的合成及生物活性  

Syntheses and Biological Activities of Novel Imine and Imide Derivatives Bearing 1,2,4-Triazole Moiety

作　　者：杨海葵 许万福[2] 段安娜[1] 游文玮[1] 赵培亮[1] 

机构地区：[1]南方医科大学药学院,广州510515 [2]南方医科大学基础医学院,广州510515

出　　处：《高等学校化学学报》2014年第3期555-563,共9页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21372113);高等学校博士学科点专项科研基金(批准号:20104433120011);广州市珠江科技新星专项资助项目(批准号:2012J2200051)资助~~

摘　　要：以取代苯甲酸为原料,经酯化、肼解、成盐和环化反应得到关键中间体4-氨基-3-芳基-1,2,4-三唑-5-硫酮,再分别与芳醛和邻苯二甲酸酐缩合得到亚胺及酰亚胺,最后经硫醚化反应合成了24个新型的含有1,2,4-三唑结构单元的亚胺及酰亚胺类化合物,其结构经质谱、红外光谱、核磁共振及元素分析确认.初步生物活性测试结果表明,在实验浓度下大部分化合物表现出一定的杀菌活性,尤其是化合物9a,9d和9e对水稻纹枯病菌的抑制活性与对照杀菌剂氟硅唑相当.初步的细胞毒性实验结果表明,化合物7c,7f和9k对人肺癌细胞(A549)的抑制活性与对照药品5-氟尿嘧啶基本处于同一水平.According to active groups combination principle, a series of novel imine and imide derivatives bearing 1,2,4-triazole moiety was designed and synthesized. The key intermediate 3-substituted phenyl-4-ami-no-1,2,4-triazole-5-thiones was synthesized by esterification, hydrazinolysis, salt and cyclization reactions, and then was condensed with aromatic aldehydes and isobenzofuran-1 , 3-dione to obtain imine and imide derivatives, which were subjected to the thioetherification with suitable halides （ RX ） to produce the corre-sponding 24 novel imine and imide derivatives bearing 1,2,4-triazole moiety. The structures of target com-pounds were fully characterized by 1 H NMR, IR, mass spectroscopy and elemental analysis. The preliminary bioassay results showed that most of the compounds possessed certain fungicidal activities. At the concentration of 150 mg/L, the inhibition rates of compounds 9a, 9d and 9e against Rhizoctonia solani were very similar with the commercial fungicide Flusilazole. Meanwhile, the preliminary structure-activity relationships（ SAR） were discussed in order to investigate the essential structures required for their bioactivities. In addition, their in vitro antitumor activities were evaluated against three cancer cell lines [ human alveolar epithelial cells （ A549 ） , human breast cancer cells （ MD-MBA-231 ） and human prostate cancer cells （ PC-3 M ） ] by the methyl thiazolyl tetrazolium（MTT） chromatometry method with Fluorouracil as a positive contrast drug. The bioassay data indicated that compounds 7c, 7f and 9k showed similar antiproliferation with Fluorouracil against A549 cell lines with IC50 values of 38.3, 44.6 and 36.7μmol/L, respectively. Most interestingly, compound 9k also exhibited a broad spectrum of antitumor activity against MCF-7 and MKN45 with IC50 values of 147.5 and 60.7 μmol/L, respectively.

关 键 词：1 2 4-三唑 杀菌活性 抗肿瘤活性 

分 类 号：O625[理学—有机化学]