苯甲酰胺类磷酸二酯酶(Ⅳ)抑制剂的设计、合成与生物活性研究  

Design, Synthesis and Biological Evaluation of Benzoyl Analogues as PDE4 Inhibitors

作　　者：冯筱晴[1] 陈意发 宋国强[1] 唐龙[1] 柯衡明 FENG Xiaoqing;CHEN Yifa;SONG Guoqiang;TANG Long;KE Hengming(School of Pharmacy,Changzhou University,Changzhou 213164,China;Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center,University of North Carolina at Chapel Hill,Chapel Hill 27514,America)

机构地区：[1]常州大学药学院,江苏常州213164 [2]美国北卡罗莱纳州立大学教堂山分校生物物理与生物化学系,教堂山27514

出　　处：《常州大学学报（自然科学版）》2021年第4期21-29,共9页Journal of Changzhou University：Natural Science Edition

基　　金：2020年度常州大学创新创业基金资助项目(2020-c-21)。

摘　　要：设计并合成磷酸二酯酶(Ⅳ)(PDE4)抑制剂,研究其酶水平的抑制活性,筛选活性较好的化合物进一步研究。通过Discovery Studio 2019设计了系列苯甲酰胺类新型小分子抑制剂;以3,4-二羟基苯甲醛为起始原料,通过醚化、氯化和氨基化等反应,合成得到了11个目标化合物;化合物经初筛后测定了其IC_(50)值。共合成11个衍生物,目标化合物的结构经^(1)H NMR,^(13)C NMR谱图确证。目标化合物的酶水平测试结果表明,化合物Cy01, Cy03, Cy04, Cy06, Cy10和Cy11均显示了微量水平的抑制活性。其中,Cy06的抑制活性IC_(50)值(PDE4)达到0.219μmol/L,值得进一步深入研究。A series of new PDE4 inhibitors were designed with the aid of Discovery Studio 2019.Then the target compounds were prepared through the etherification,chlorination and ammonification reaction with 3,4-dihydroxybenzaldehyde as initial material.All of the derivatives were evaluated for their anti-PDE4 activities.After preliminary screening of the 11 newly synthesized PDE4 inhibitors,the compounds(Cy01,Cy03,Cy04,Cy06,Cy10 and Cy11)which showed activity were further tested for their IC 50 value by kit method.Among them,Cy06 indicated the best activity with the IC_(50)(PDE4)=0.219μmol/L which needed to be further investigated.The preliminary structure-activity relationship was summarized.

关 键 词：磷酸二酯酶Ⅳ型(PDE4)抑制剂 Discovery Studio 2019 生物活性检测 

分 类 号：R914.5[医药卫生—药物化学]