中文摘要：

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2.0μM。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q^2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。

英文摘要：

A series of 1,3-disubstituted-pyridin-4（1H）-one derivatives were synthesized. The results of a viability assay on NIH_T3 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 q~2 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.