Synthesis And Quantitative Structure–activity Relationships Study For Phenylpropenamide Derivatives As Inhibitors Of Hepatitis B Virus Replication

Hepatitis B virus is a kind of DNA virus.The asymptomatic hepatitis B virus carriers are approaching three hundred million people in the world.Hepatitis B has become an incurable disease.Thus,a drug against HBV study has a great significance.A series of phenylpropenamide derivatives with anti-hepatitis B virus activities were reported in our research group.Their quantitative structure-activity relationships（QSAR）of phenylpropenamide compound had been studied,parameters for constructing the QSAR models,whether they could be applied to different structural units is a question.Therefor,a series of new arylpropenamide derivatives were designed with a modified arylpropenamide B ring.The structure of target compounds was characterized by carbon nuclear magnetic resonance spectroscopy(¹³C NMR),hydrogen nuclear magnetic resonance spectroscopy（¹H NMR）,high resolution mass spectrum（HRMS）,mass spectrometry（MS）and infrared absorption spectroscopy（IR）.The anti-hepatitis B virus（HBV）activities of phenylpropenamide derivatives were evaluated used EC⁵⁰ as parameter.A new and more accurate QSAR equations were constructed used the thermal energy（TE）and entropy(S^?)of arylpropenamides of vinyl bromides compounds and chloro-substitude propenamides compounds as parameters,and the QSAR equations could be constructed.The QSAR equations possessed relatively high correlation coefficient with R²=0.6610 and better 31.19704 F-statistics,and least number of variables.Because of the new equations based on more comprehensive substrates,so they have stronger biological activity prediction ability and more extensive application capabilities.In this study,a new and more representatively 3D-QSAR were constructed using the CoMFA performed.The model had a high R²（0.931 and 0.923）respectively for bromides compounds and chloro-substitude propenamides compounds with a low standard deviation（SE,0.177 and 0.238,respectively）and a high Fischer ratio（F,78.414 and 69.721,respectively）.A QSAR model is generally acceptable if R² is approximately 0.8 or higher.Specially,the cross-validation related coefficient q² is 0.604 and 0.563 respectively（>0.5）,suggesting a good prediction ability of this model.The new 2D or 3D QSAR models could be successfully be utilized to predict the anti-HBV activities of the arylpropenamide molecules to provide some reference value for future research.