Synthesis and quantitative structure–activity relationships study for phenylpropenamide derivatives as inhibitors of hepatitis B virus replication

•New phenylpropenamide derivatives were synthesized and characterized.•Their 2D-QSAR and model 3D-QSAR were estabilished on DFT and SYBYL respectively.•QSAR model illustrated the effect of substituent on anti-HBV activities.

A series of new phenylpropenamide derivatives containing different substituents was synthesized, characterized and evaluated for their anti-hepatitis B virus (HBV) activities. The quantitative structure–activity relationships (QSAR) of phenylpropenamide compound have been studied. The 2D-QSAR models, based on DFT and multiple linear regression analysis methods, revealed that higher values of total energy (TE) and lower entropy (Sө) enhanced the anti-HBV activities of the phenylpropenamide molecules. Predictive 3D-QSAR models were established using SYBYL multifit molecular alignment rule. The optimum models were all statistically significant with cross-validated and conventional coefficients, indicating that they were reliable enough for activity prediction.

Graphical abstractThe new phenylpropenamide derivatives were synthesized, characterized and evaluated for their anti-HBV activities. The 2D and 3D-QSAR models of phenylpropenamide was constructed.Figure optionsDownload full-size imageDownload as PowerPoint slide