Ligand-based QSAR Studies on the Indolinones Derivatives as Inhibitors of the Protein Tyrosine Kinase of Fibroblast Growth Factor Receptor by CoMFA and CoMSIA

Department of Chemistry, Inha University, Incheon 402-751, KoreaReceived June 30, 2004Ligand-based quantitative structure-activity relationship (QSAR) studies were performed on indolinonesderivatives as a potential inhibitor of the protein tyrosine kinase of fibroblast growth factor receptor (FGFR) bycomparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis(CoMSIA) implemented in the SYBYL packages. The initial X-ray structure of docked ligand (Su5402) toFGFR was used to minimize the 27 training set molecules using TRIPOS force field. Seven models weregenerated using CoMFA and CoMSIA with grid spacing 2 A. After the PLS analysis the best predictedCoMSIA model with hydrophobicity, hydrogen bond donor and acceptor property showed that a leave-one out(LOO) cross validated value (r