QSAR studies of sulfonamide analogs containing thiazolone as hepatisis C virus NS5B polymerase inhibitor

In this study, a 2D-QSAR analysis was carried out by using 57 thiazolone derivatives synthesized by Yao et.al.. These thiazolones prevent the replication of Hepatitis C Virus by NS5B polymerase inhibition. Firstly, the compounds were optimized with PM3, Hatree-Fock/3-21G(d,p) and DFT/B3LYP/6-31G(d,p) methods. Then, the compounds were seperated into 3 groups and for each groups QSAR models with 7 descriptors developed by Heuristic Method (HM) and The Best Multi-Linear Regression (BMLR) encoded in CODESSA software. The obtaining 18 descriptors were used to develop general QSAR models. The general QSAR model obtained with DFT/B3LYP/6-31G(d,p) basic set and BMLR method have the most predicted corelation coefficients. It indicates that Hydrogen Acceptor Charge Area-2, ZX Shadow, Minimum nucleophilic reaction index for an N atom, Average valency of an H atom, Polarity parameter, XY Shadow and Min (>0.1) bond order of a C atom were the most significant parameters for the inhibition of NS5B polymerase. QSAR model predict that inhibition activitiy increases if the compounds have lower hydrogen bond acceptor capacity and molecules have elongated geometry.Key Words : QSAR, thiazolone, sülfonamide, HCV NS5B polymerase.