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
S. Moro, M. Bacilieri, B. Cacciari, C. Bolcato, C. Cusan, G. Pastorin, K. Klotz, and G. Spalluto. Bioorg Med Chem, 14 (14):
4923-32(July 2006)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..
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.
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
%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
}