title: 3D-QSAR study of tetrahydro-3H-imidazo[4,5-c]pyridine derivatives as VEGFR-2 kinase inhibitors using various charge schemes.
abstract: Vascular endothelial growth factor-2 receptor (VEGFR-2) kinase is a promising target for the development of novel anticancer drugs. Three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on a series of tetrahydro-3H-imidazo[4,5-c]pyridine derivatives to understand the structural basis for VEGFR-2 inhibitory activity. Several 3D-QSAR models were developed using various partial atomic charge schemes. Comparative molecular field analysis (CoMFA) and Comparative molecular similarity indices analysis (CoMSIA) methods were employed to derive these models. The CoMFA models performed better than the CoMSIA models. The reliable CoMFA model was obtained with the Gasteiger-Marsili charge scheme. The model produced statistically significant results with a cross-validated correlation coefficient (q(2)) of 0.635 and a coefficient of determination (r(2)) of 0.930. The model showed reasonable predictive power with predictive correlation coefficient ([Formula: see text]) of 0.582. Robustness of the model was further checked by leave-five-out cross-validation, bootstrapping and progressive scrambling analysis. The model was found to be statistically robust and expected to assist in the design of novel compounds with enhanced VEGFR-2 inhibitory activity.
authors: Department of Bio-New Drug Development, College of Medicine, Chosun University, Gwangju, 501-759, Republic of Korea.
authors: Anand
authors: A
authors: Balupuri
authors: Pavithra K
authors: PK
authors: Balasubramanian
authors: Seung Joo
authors: SJ
authors: Cho
mesh_terms: D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D040301:Vascular Endothelial Growth Factor Receptor-2