title: Pyrrolo[3,2-d]pyrimidine derivatives as type II kinase insert domain receptor (KDR) inhibitors: CoMFA and CoMSIA studies.
abstract: Kinase insert domain receptor (KDR) inhibitors have been proved to be very effective anticancer agents. Molecular docking, 3D-QSAR methods, CoMFA and CoMSIA were performed on pyrrolo[3,2-d]pyrimidine derivatives as non-ATP competitive KDR inhibitors (type II). The bioactive conformation was explored by docking one potent compound 20 into the active site of KDR in its DFG-out inactive conformation. The constructed CoMFA and CoMSIA models produced statistically significant results with the cross-validated correlation coefficients q(2) of 0.542 and 0.552, non-cross-validated correlation coefficients r(2) of 0.912 and 0.955, and predicted correction coefficients r(2) (pred) of 0.913 and 0.897, respectively. These results ensure the CoMFA and CoMSIA models as a tool to guide the design of a series of new potent KDR inhibitors.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yuan-Xin
authors.initials: YX
authors.lastname: Tian
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C450639:Pyrrolo(2,3-d)pyrimidine; D040301:Vascular Endothelial Growth Factor Receptor-2