[1]冯筱晴,陈意发,宋国强,等.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[J].常州大学学报(自然科学版),2021,33(04):21-29.[doi:10.3969/j.issn.2095-0411.2021.04.004]
　FENG Xiaoqing,CHEN Yifa,SONG Guoqiang,et al.Design, Synthesis and Biological Evaluation of Benzoyl Analogues as PDE4 Inhibitors[J].Journal of Changzhou University(Natural Science Edition),2021,33(04):21-29.[doi:10.3969/j.issn.2095-0411.2021.04.004]
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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()
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常州大学学报(自然科学版)[ISSN:2095-0411/CN:32-1822/N]

卷:
第33卷
期数:
2021年04期
页码:
21-29
栏目:
生物医药工程
出版日期:
2021-07-28

文章信息/Info

Title:
Design, Synthesis and Biological Evaluation of Benzoyl Analogues as PDE4 Inhibitors
文章编号:
2095-0411(2021)04-0021-09
作者:
冯筱晴1;  陈意发1;  宋国强1;  唐 龙1;  柯衡明2
(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)
Author(s):
FENG Xiaoqing1;  CHEN Yifa1;  SONG Guoqiang1;  TANG Long1;  KE Hengming2
(1. School of Pharmacy, Changzhou University, Changzhou 213164, China; 2. Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill 27514, America)
关键词:
磷酸二酯酶IV型(PDE4)抑制剂;  Discovery Studio 2019;  生物活性检测
Keywords:
phosphodiesterase IV(PDE4)inhibitors;  Discovery Studio 2019;  activity evaluation
分类号:
R 914.5
DOI:
10.3969/j.issn.2095-0411.2021.04.004
文献标志码:
A
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IC50值。共合成11个衍生物, 目标化合物的结构经1H NMR, 13C 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IC50值(PDE4)达到0.219 μmol/L, 值得进一步深入研究。
Abstract:
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 IC50 value by kit method. Among them, Cy06 indicated the best activity with the IC50(PDE4)= 0.219 μmol/L which needed to be further investigated. The preliminary structure-activity relationship was summarized.

参考文献/References:

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备注/Memo

备注/Memo:
收稿日期:2020-11-21。基金项目:2020年度常州大学创新创业基金资助项目(2020-c-21)。作者简介:冯筱晴(1974—), 女, 山东青岛人, 博士, 讲师。E-mail:fxqfw@163.com
更新日期/Last Update: 1900-01-01