5-苯基-1,2,4-噁二唑衍生物的合成及其作为乙酰辅酶A羧化酶抑制剂的生物活性  

Synthesis of 5-Phenyl-1,2,4-oxadiazole Derivatives and TheirBiological Activities As Inhibitors of Acetyl-CoA Carboxylase

作　　者：王婕 袁家英 杨奕 刘文雅 钱茹雨 黄统辉 WANG Jie;YUAN Jiaying;YANG Yi;LIU Wenya;QIAN Ruyu;HUANG Tonghui(Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,XuZhou Medical University,XuZhou 221000,China)

机构地区：[1]徐州医科大学江苏省新药研究与临床药学重点实验室,江苏徐州221000

出　　处：《合成化学》2024年第5期451-456,共6页Chinese Journal of Synthetic Chemistry

基　　金：江苏省大学生创新创业计划训练项目(202210313042Z)。

摘　　要：乙酰辅酶A羧化酶(Acetyl-CoA Carboxylase,ACC)是一种脂肪酸合成限速酶,是肿瘤治疗的热门靶点之一。本文以3-氯苯胺和亚甲基丁二酸为起始原料,经环化、缩合和酰胺化等反应获得了一系列5-苯基-1,2,4-噁二唑类化合物(9a~9i),其中,化合物9a、9b、9e~9h为全新结构,经^(1)H MNR、^(13)C MNR和MS(ESI)进行了表征。通过Molsoft软件计算目标化合物9a~9i的脂水分配系数和类药性分数,使用ADP-Glo^(TM)激酶检测试剂盒检测化合物ACC抑制活性。结果表明:化合物9g在10μM浓度下对ACC抑制活性达到95.26%,与阳性对照药CP-640186相当。Acetyl-Coa Carboxylase(ACC)is a kind of fatty acid synthesis rate-limiting enzyme,which is one of the hot targets of tumor therapy.A series of novel 5-phenyl-1,2,4-oxadiazoles(9a~9i)were obtained through cyclization,condensation,amidation using 3-chloroaniline and methylenesuccinic acid as the starting materials.The novel compounds of 9a,9b,9e~9h were characterized by ^(1)H MNR,^(13)C MNR and MS(ESI).The lipid-water partition coefficients and drug-likeness scores of the target compounds 9a~9i were calculated by Molsoft online software,the acetyl-CoA carboxylase(ACC)inhibitory activity of the compounds was detected by the ADP-Glo ^(TM)kinase assay kit.The results showed that the inhibitory activity of compound 9g on ACC reached 95.26%at the concentration of 10μM,which was comparable with that of positive control drug CP-640186.

关 键 词：5-苯基-1 2 4-噁二唑衍生物 乙酰辅酶A羧化酶 抑制剂 抑制活性 

分 类 号：R914.4[医药卫生—药物化学]