1,3-二取代-4-吡啶酮类衍生物的合成、活性及定量构效关系研究

doi:10.5246/jcps.2016.06.045

中国药学(英文版) ›› 2016, Vol. 25 ›› Issue (6): 395-407.DOI: 10.5246/jcps.2016.06.045

• 【研究论文】 • 下一篇

1,3-二取代-4-吡啶酮类衍生物的合成、活性及定量构效关系研究

彭娟^1#, 李乾斌^1#, 向红琳², 王泽瑜¹, 胡高云^1*

1. 中南大学药学院药物化学系, 湖南长沙 40013
2. 湖南师范大学医学院药学系, 湖南长沙 40013

收稿日期:2015-12-25 修回日期:2016-03-26 出版日期:2016-06-29 发布日期:2016-04-12
通讯作者: #These authors contribute equally to this work. *Corresponding author. Tel.: +86-0731-82650371, E-mail: hugaoyun@csu.edu.cn
基金资助:
National Nature Science Foundation of China (Grant No. 21172268).

Synthesis, anti-fibrosis activity, and quantitative structure-activity relationship studies of 1,3-disubstituted-pyridin-4(1H)-one derivatives

Juan Peng^1#, Qianbin Li^1#, Honglin Xiang², Zeyu Wang¹, Gaoyun Hu^1*

1. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
2. Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha 410013, China

Received:2015-12-25 Revised:2016-03-26 Online:2016-06-29 Published:2016-04-12
Contact: #These authors contribute equally to this work. *Corresponding author. Tel.: +86-0731-82650371, E-mail: hugaoyun@csu.edu.cn
Supported by:
National Nature Science Foundation of China (Grant No. 21172268).

摘要/Abstract

摘要：

本论文设计合成了30个1,3-二取代-4-吡啶酮类衍生物。NIH₃T₃细胞增殖抑制实验结果显示化合物3m的半数抑制率IC₅₀值为2.0 μM。分别用topomer CoMFA和AutoGPA方法对所有目标化合物进行三维定量构效关系研究,所得到的模型交叉验证相关系数q²分别为0.662和0.787。研究结果表明, 3-羟基-4-吡啶酮可作为抗纤维化药物研究的新型骨架。此外,基于活性数据所获得的3D-QSAR和药效团模型为4-吡啶酮类抗纤维化化合物的结构优化提供了新的思路。

关键词: 4-吡啶酮, 定量构效关系, 抗纤维化药物

Abstract:

A series of 1,3-disubstituted-pyridin-4(1H)-one derivatives were synthesized. The results of a viability assay on NIH₃T₃ cells indicated that compound 3m potently inhibited the cell viability with an IC₅₀ value of 2.0 μM. The 3D-quantitative structure-activity relationship analyses of 30 final molecules applying topomer CoMFA and AutoGPA methods gave two reasonable models with a cross-validated correlation coefficient q² of 0.662 and 0.787, respectively. The achievement herein suggested the application of 3-hydroxypyridin-4(1H)-one as a novel scaffold for the discovery of anti-fibrosis agents. In addition, the QSAR and pharmacophore models established with the activity data may provide new insights into the structure optimization of pyridin-4(1H)-one derivative with potent anti-fibrotic effects.

Key words: Pyridin-4(1H)-one, QSAR, Anti-fibrosis agents

中图分类号:

R916

Supporting:

彭娟, 李乾斌, 向红琳, 王泽瑜, 胡高云. 1,3-二取代-4-吡啶酮类衍生物的合成、活性及定量构效关系研究[J]. 中国药学(英文版), 2016, 25(6): 395-407.

Juan Peng, Qianbin Li, Honglin Xiang, Zeyu Wang, Gaoyun Hu. Synthesis, anti-fibrosis activity, and quantitative structure-activity relationship studies of 1,3-disubstituted-pyridin-4(1H)-one derivatives[J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(6): 395-407.

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1,3-二取代-4-吡啶酮类衍生物的合成、活性及定量构效关系研究

Synthesis, anti-fibrosis activity, and quantitative structure-activity relationship studies of 1,3-disubstituted-pyridin-4(1H)-one derivatives

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