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Cluster Analysis and QSAR Study of Some Anti‐hepatitis B Virus Agents Comprising 4‐Aryl‐6‐chloro‐quinolin‐2‐ones and 5‐Aryl‐7‐chloro‐1,4‐benzodiazepines
Author(s) -
Li Zuguang,
Chen Kexian,
Xie Haiying,
Wang Yan,
Dong Fengchao
Publication year - 2009
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201090007
Subject(s) - quantitative structure–activity relationship , chemistry , steric effects , aryl , hepatitis b virus , homo/lumo , stereochemistry , virus , computational biology , combinatorial chemistry , virology , molecule , organic chemistry , biology , alkyl
Chronic hepatitis B virus (HBV) infection has caused a global health crisis by infecting more than 400 million people, constituting the ninth leading cause of death in the world. There is an urgent demand for antiviral agents to effectively inhibit HBV infection based on the development of drug resistance and increasing infected numbers. Quantitative structure‐activity relationship (QSAR) models were developed for a series of potent anti‐hepatitis B virus agents comprising 4‐aryl‐6‐chloro‐quinolin‐2‐ones and 5‐aryl‐7‐chloro‐1,4‐benzodiazepines using Cerius 2 4.10 software. The best 2D‐QSAR model ( r 2 =0.952 and r 2 pred =0.989) constructed by the genetic function approximation (GFA) methodology indicates that the activity was mainly governed by E‐State‐keys (S_sssN and S_sCl), electronic descriptor (LUMO), thermodynamic descriptor (Foct) and conformational descriptor (Energy). 3D‐QSAR models were developed based on steric and electrostatic interactions by molecular field analysis (MFA) to investigate the substitutional requirements for the favorable receptor‐drug interaction, showing that electrostatic interactions is crucial for the activity. The models derived can provide a preliminary valuable guidance for continuing search for novel potent anti‐hepatitis B virus agents prior to synthesis.