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

doi:10.5246/jcps.2016.06.045

Journal of Chinese Pharmaceutical Sciences ›› 2016, Vol. 25 ›› Issue (6): 395-407.DOI: 10.5246/jcps.2016.06.045

• Original articles • Next Articles

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).

Abstract

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

CLC Number:

R916

Supporting:

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

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