2-取代苯基-5-取代苯甲酰胺基-1,3,4-噻二唑的合成、抑菌活性及三维定量构效关系  

Synthesis,fungicidal activities and three dimensional quantitative structure-activity relationship of 2-substituted phenyl-5-substituted benzamide-1,3,4-thiadiazole

作　　者：王三艳 彭雅琦 娄佳玉 王美怡 WANG Sanyan;PENG Yaqi;LOU Jiayu;WANG Meiyi(College of Chemical Engineering and Materials Science,Tianjin University of Science and Technology,Tianjin 300457,China)

机构地区：[1]天津科技大学化工与材料学院,天津300457

出　　处：《农药学学报》2022年第4期732-742,共11页Chinese Journal of Pesticide Science

基　　金：国家自然科学基金项目(21262001);天津科技大学基本科研业务费(2019KJ223).

摘　　要：以取代苯甲酸为起始原料,与氨基硫脲、三氯氧磷及取代苯甲酰氯进行缩合,制备了33个2-取代苯基-5-取代苯甲酰胺基-1,3,4-噻二唑E_(1)~E_(33)。采用核磁共振氢谱(^(1)H NMR)和高分辨质谱(HRMS)等对目标化合物的结构进行了确证及表征。采用菌丝生长速率法测定了目标化合物对根霉Rhizopus nigricans、青霉Penicillium glaucum、灰霉Botrytis cinerea、交链孢霉Alternaria brassicae和黑曲霉Aspergillus niger的体外抑菌活性。针对黑曲霉的抑制活性,分别利用CoMFA和CoMSIA对目标化合物进行了初步的三维定量构效关系(3D-QSAR)研究。结果表明,大部分化合物表现出良好的抑菌活性,在50μg/mL下,化合物E_(1)、E_(2)和E_(29)对供试真菌的抑制率均达到80%以上,与对照药剂百菌清和多菌灵的抑菌效果相当。综合两种模型的结果,发现静电场的贡献值高于其他势场,且当苯环a的4位引入供电子基、苯环a的2位和6位以及苯环b上引入吸电子基时,有利于化合物抑菌活性的提高,可为进一步指导设计合成此类高活性化合物提供理论依据。Thirty-three different 2-substituted phenyl-5-substituted benzamide-1,3,4-thiadiazole E_(1)-E_(33) were prepared by reaction of substituted benzoic acid with thiosemicarbazone,phosphorus oxychloride and substituted benzoyl chloride.The structure of the target compounds were confirmed and characterized by proton nuclear magnetic resonance(1H NMR)and high resolution mass spectroscopy(HRMS).Fungicidal activities of target compounds against Rhizopus nigricans,Penicillium glaucum,Botrytis cinerea,Alternaria brassicae and Aspergillus niger in vitro were studied with the mycelial growth rate method.A preliminary three-dimensional quantitative structure-activity relationship(3DQSAR)of the target compounds against A.niger was carried out using CoMFA and CoMSIA.The results showed that most of the compounds showed good inhibitory activity,especially at the concentration of 50μg/mL,the inhibitory rates of compounds E_(1),E_(2) and E_(29) against the tested fungi were more than 80%,which were equivalent to that of the control pesticides,chlorothalonil and carbendazim.The results of the two models are combined to draw the conclusion:the effect of electrostatic field is higher than that of other potential fields.It was advantageous to enhance the fungicidal activity of the compounds when the benzene ring a introduces electron-donating group into 4-position,the 2 and 6-positions of benzene ring a and benzene ring b introduces electron-withdrawing group.The conclusions can provide insight into further design of highly antifungal title compounds.

关 键 词：1 3 4-噻二唑 酰胺衍生物 抑菌活性 三维定量构效关系(3D-QSAR) 

分 类 号：TQ455.4[化学工程—农药化工]