Universidad Peruana Cayetano Heredia

Docking and quantitative structure-activity relationship studies for 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)aniline, 3-fluoro-4-(1H- pyrrolo[2,3-b]pyridin-4-yloxy)aniline, and 4-(4-amino-2-fluorophenoxy)-2- pyridinylamine derivatives as c-Met kinase inhibitors

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dc.contributor.author Caballero, J.
dc.contributor.author Quiliano, M.
dc.contributor.author Alzate-Morales, J.H.
dc.contributor.author Zimic-Peralta, Mirko Juan
dc.contributor.author Deharo, E.
dc.date.accessioned 2022-01-18T19:26:44Z
dc.date.available 2022-01-18T19:26:44Z
dc.date.issued 2011
dc.identifier.uri https://hdl.handle.net/20.500.12866/10826
dc.description.abstract We have performed docking of 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4- yloxy)aniline (FPTA), 3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline (FPPA), and 4-(4-amino-2-fluorophenoxy)-2-pyridinylamine (AFPP) derivatives complexed with c-Met kinase to study the orientations and preferred active conformations of these inhibitors. The study was conducted on a selected set of 103 compounds with variations both in structure and activity. Docking helped to analyze the molecular features which contribute to a high inhibitory activity for the studied compounds. In addition, the predicted biological activities of the c-Met kinase inhibitors, measured as IC50 values were obtained by using quantitative structure-activity relationship (QSAR) methods: Comparative molecular similarity analysis (CoMSIA) and multiple linear regression (MLR) with topological vectors. The best CoMSIA model included steric, electrostatic, hydrophobic, and hydrogen bond-donor fields; furthermore, we found a predictive model containing 2D-autocorrelation descriptors, GETAWAY descriptors (GETAWAY: Geometry, Topology and Atom-Weight AssemblY), fragment-based polar surface area (PSA), and MlogP. The statistical parameters: cross-validate correlation coefficient and the fitted correlation coefficient, validated the quality of the obtained predictive models for 76 compounds. Additionally, these models predicted adequately 25 compounds that were not included in the training set. en_US
dc.language.iso eng
dc.publisher Springer
dc.relation.ispartofseries Journal of Computer-Aided Molecular Design
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Controlled Study en_US
dc.subject Unclassified Drug en_US
dc.subject Models Molecular en_US
dc.subject Enzyme Inhibition en_US
dc.subject Molecular Structure en_US
dc.subject Drug Structure en_US
dc.subject Drug Mechanism en_US
dc.subject IC 50 en_US
dc.subject Enzyme Active Site en_US
dc.subject Validation Process en_US
dc.subject Prediction en_US
dc.subject Drug Protein Binding en_US
dc.subject Complex Formation en_US
dc.subject Process Development en_US
dc.subject 3 Fluoro 4 (1h Pyrrolo[23 B]Pyridin 4 Yloxy)Aniline Derivative en_US
dc.subject 3 Fluoro 4 (Pyrrolo[21 F][124]Triazin 4 Yloxy)Aniline Derivative en_US
dc.subject 4 (4 Amino 2 Fluorophenoxy) 2 Pyridinylamine Derivative en_US
dc.subject Aminopyridines en_US
dc.subject Aniline Compounds en_US
dc.subject C-Met Kinase Inhibitors en_US
dc.subject Comparative Molecular Similarity Indices Analysis en_US
dc.subject Comsia en_US
dc.subject Conformation en_US
dc.subject Data Analysis Software en_US
dc.subject Hydrogen Bonding en_US
dc.subject Hydrophobicity en_US
dc.subject Molecular Conformation en_US
dc.subject Molecular Docking en_US
dc.subject Multiple Linear Regression Analysis en_US
dc.subject Protein Kinase Inhibitors en_US
dc.subject Proto-Oncogene Proteins C-Met en_US
dc.subject Pyrroles|Quantitative Structure-Activity Relationship en_US
dc.subject Receptors Growth Factor en_US
dc.subject Scatter Factor Receptor en_US
dc.subject Static Electricity en_US
dc.subject Topological Descriptors en_US
dc.title Docking and quantitative structure-activity relationship studies for 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)aniline, 3-fluoro-4-(1H- pyrrolo[2,3-b]pyridin-4-yloxy)aniline, and 4-(4-amino-2-fluorophenoxy)-2- pyridinylamine derivatives as c-Met kinase inhibitors en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1007/s10822-011-9425-1
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.00
dc.relation.issn 1573-4951


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