%0 Journal Article %1 Moro2006 %A Moro, S. %A Bacilieri, M. %A Cacciari, B. %A Bolcato, C. %A Cusan, C. %A Pastorin, G. %A Klotz, K. N. %A Spalluto, G. %D 2006 %J Bioorg Med Chem %K & A3/*antagonists Adenosine Analysis Binding Chemistry Combinatorial Conformation Design Drug Electricity Humans Interface Least-Squares Models, Molecular Protein Pyrimidines/chemical Quantitative Relationship Sites Static Structure-Activity Techniques User-Computer inhibitors/chemistry synthesis/chemistry/pharmacology Receptor %N 14 %P 4923-32 %T The application of a 3D-QSAR (autoMEP/PLS) approach as an efficient pharmacodynamic-driven filtering method for small-sized virtual library: application to a lead optimization of a human A3 adenosine receptor antagonist %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16564691 %V 14 %X We have recently reported that the combination of molecular electrostatic potential (MEP) surface properties (autocorrelation vectors) with the conventional partial least squares (PLS) analysis can be used to produce a robust ligand-based 3D structure-activity relationship (autoMEP/PLS) for the prediction of the human A3 receptor antagonist activities. Here, we present the application of the 3D-QSAR (autoMEP/PLS) approach as an efficient and alternative pharmacodynamic filtering method for small-sized virtual library. For this purpose, a small-sized combinatorial library (841 compounds) was derived from the scaffold of the known human A3 antagonist pyrazolo-triazolo-pyrimidines. The most interesting analogues were further prioritized for synthesis and pharmacological characterization. Remarkably, we have found that all the newly synthetized compounds are correctly predicted as potent human A3 antagonists. In particular, two of them are correctly predicted as sub-nanomolar inhibitors of the human A3 receptor.

@article{Moro2006, abstract = {We have recently reported that the combination of molecular electrostatic potential (MEP) surface properties (autocorrelation vectors) with the conventional partial least squares (PLS) analysis can be used to produce a robust ligand-based 3D structure-activity relationship (autoMEP/PLS) for the prediction of the human A3 receptor antagonist activities. Here, we present the application of the 3D-QSAR (autoMEP/PLS) approach as an efficient and alternative pharmacodynamic filtering method for small-sized virtual library. For this purpose, a small-sized combinatorial library (841 compounds) was derived from the scaffold of the known human A3 antagonist pyrazolo-triazolo-pyrimidines. The most interesting analogues were further prioritized for synthesis and pharmacological characterization. Remarkably, we have found that all the newly synthetized compounds are correctly predicted as potent human A3 antagonists. In particular, two of them are correctly predicted as sub-nanomolar inhibitors of the human A3 receptor.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Moro, S. and Bacilieri, M. and Cacciari, B. and Bolcato, C. and Cusan, C. and Pastorin, G. and Klotz, K. N. and Spalluto, G.}, biburl = {https://www.bibsonomy.org/bibtex/29f598bfe66ebbc1563a0b2d1ae2dc91c/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {ad8cec2a3461b0600316e2965daf79bb}, intrahash = {9f598bfe66ebbc1563a0b2d1ae2dc91c}, issn = {0968-0896 (Print) 0968-0896 (Linking)}, journal = {Bioorg Med Chem}, keywords = {& A3/*antagonists Adenosine Analysis Binding Chemistry Combinatorial Conformation Design Drug Electricity Humans Interface Least-Squares Models, Molecular Protein Pyrimidines/chemical Quantitative Relationship Sites Static Structure-Activity Techniques User-Computer inhibitors/chemistry synthesis/chemistry/pharmacology Receptor}, month = {Jul 15}, note = {Moro, Stefano Bacilieri, Magdalena Cacciari, Barbara Bolcato, Chiara Cusan, Claudia Pastorin, Giorgia Klotz, Karl-Norbert Spalluto, Giampiero In Vitro Research Support, Non-U.S. Gov't England Bioorganic \& medicinal chemistry Bioorg Med Chem. 2006 Jul 15;14(14):4923-32. Epub 2006 Mar 29.}, number = 14, pages = {4923-32}, shorttitle = {The application of a 3D-QSAR (autoMEP/PLS) approach as an efficient pharmacodynamic-driven filtering method for small-sized virtual library: application to a lead optimization of a human A3 adenosine receptor antagonist}, timestamp = {2010-12-14T18:20:21.000+0100}, title = {The application of a 3D-QSAR (autoMEP/PLS) approach as an efficient pharmacodynamic-driven filtering method for small-sized virtual library: application to a lead optimization of a human A3 adenosine receptor antagonist}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16564691}, volume = 14, year = 2006 }