Molecular Modeling and Prediction of Bioactivity

489 Pages·2000·25.366 MB·English

by  James P. Snyder, Forrest D. Snyder (auth.), Klaus Gundertofte, Flemming Steen Jørgensen (eds.)

Molecular Modeling and
Prediction of Bioactivity
Edited by
Klaus Gundertofte
H. Lundbeck AIS
Valby, Denmark
and
Flemming Steen Jf,?)rgensen
Royal Danish School of Pharmacy
Copenhagen, Denmark
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging-in-Publication Data
Molecular modeling and prediction ofbioaetivity / edited by Klaus Gundertofte and
Flemming Steen J0rgensen.
p.em.
"Proceedings ofthe 12th European Symposium on Quantitative Structure-Activity
Relationships ... held August 23-28,1998, in Copenhagen, Denmark"--CIP copyright p.
Includes bibiiographical referenees and index.
ISBN 978-1-4613-6857-1 ISBN 978-1-4615-4141-7 (eBook)
DOI 10.1007/978-1-4615-4141-7
1. QSAR (Biochemistry)--Congresses. 2. Drugs--Desigu--Congresses. 3.
Biomolecules--Computer simulation--Congresses. 1. Gundertofte, Klaus. II. Jerrgensen,
Flennning S. m. European Symposium on Quantitative Structure-Activity Relationships
(12th: 1998: Copenhagen, Demnark)
RM301.42 .M64 1999
6IS'.19--dc21
99-044859
Proceedings of the 12th European Symposium on Quantitative Structure-Activity Relationships: Molecular
Modeling and Prediction of Bioactivity, held August 23-28,1998, in Copenhagen, Denmatk
ISBN 978-1-4613-6857-1
© 2000 Springer Science+Business Media New York
Originally published by Kluwer Academic/Plenum Publishers in 2000
http://www.wkap.nl
ro 9 8 7 6 5 432
A C.I.P. record for this book is available from the Library of Congress
Ali rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any
means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission
from the Publisher

Design and Activity Estimation of a New Class of Analgesics ............................................. 195
Slavomir Filipek and Danuta Pawlak
Unified Pharmacophoric Model for Cannabinoids and Aminoalkylindoles .......................... 201
Joong-Youn Shim, Elizabeth R. Coli antes, William J. Welsh, and Allyn C. Howlett
Chemometric Detection of Binding Sites of7TM Receptors ................................................ 207
Monica Clementi, Sara Clementi, Sergio Clementi, Gabriele Cruciani,
Manuel Pastor, and Jonas E. Nilsson
Section VII: New Methods in Drug Discovery
SpecMat: Spectra as Molecular Descriptors for the Prediction of Biological Activity ......... 215
R. Bursi and V.J. van Geerestein
Hydrogen Bond Contributions to Properties and Activities of Chemicals and Drugs .......... 221
Oleg A. Raevsky, Klaus J. Schaper, Han van de Waterbeemd,
and James W. McFarland
Section VIII: Modeling of Membrane Penetration
Predicting Peptide Absorption ............................................................................................... 231
Lene H. Kramp, Anders Berglund, Maria Sandberg, Inge Th~ger Christensen,
Lars Hovgaard, and Sven Frokjaer
Physicochemical High Throughput Screening (pC-HTS): Determination of Membrane
Permeability, Partitioning and Solubility .................................................................. 237
Manfred Kansy, Krystyna Kratzat, Isabelle Parrilla, Frank Senner,
and Bjorn Wagner
Understanding and Estimating MembranelWater Partition Coefficients: Approaches to
Derive Quantitative Structure Property Relationships ............................................... 245
Wouter H. J. Vaes, Efiaut Urrestarazu Ramos, Henk J. M. Verhaar,
Christopher J. Cramer, and Joop L. M. Hermens
Prediction of Human Intestinal Absorption of Drug Compounds from Molecular
Structure ..................................................................................................................... 249
M. D. Wessel, P. C. Jurs, J. W. Tolan, and S. M. Muskal
Section IX: Poster Presentations
Poster Session I: New Developments and Applications of Multivariate QSAR
Free-Wilson-Type QSAR Analyses Using Linear and Nonlinear Regression Techniques ... 261
Klaus-Jiirgen Schaper
QSAR Studies of Picrodendrins and Related Terpenoids-Structural Differences
between Antagonist Binding Sites on GABA Receptors of Insects and Mammals .. 263
Miki Akamatsu, Yoshihisa Ozoe, Taizo Higata, Izumi Ikeda, Kazuo Mochida,
Kazuo Koike, Taichi Ohmoto, Tamotsu Nikaido, and Tamio Ueno
Molecular Lipophilicity Descriptors: A Multivariate Analysis ............................................. 265
Raimund Mannhold and Gabriele Cruciani
ix
World Wide Web-Based Calculation of Substituent Parameters for QSAR Studies ............ 267
PeterErtl
COMBINE and Free-Wilson QSAR Analysis of Nuclear Receptor-DNA Binding ............. 269
Sanja Tomic, Lennart Nilsson, and Rebecca C. Wade
QSAR Model Validation ....................................................................................................... 271
Erik Johansson, Lennart Eriksson, Maria Sandberg, and Svante Wold
QSPR Prediction of Henry's Law Constant: Improved Correlation with New Parameters .. 273
John C. Dearden, Shazia A. Ahmed, Mark T. D. Cronin, and Janeth A. Sharra
QSAR of a Series of Camitine Acetyl Transferase (CAT) Substrates .................................. 275
G. Gallo, M. Mabilia, M. Santaniello, M. O. Tinti, and P. Chiodi
"Classical" and Quantum Mechanical Descriptors for Phenolic Inhibition of Bacterial
Growth ....................................................................................................................... 277
S. Shapiro and D. Turner
Hydrogen Bond Acceptor and Donor Factors, C. and Cd: New QSAR Descriptors .............. 280
James W. McFarland, Oleg A. Raevsky, and Wendell W. Wilkerson
Development and Validation of a Novel Variable Selection Technique with Application
to QSAR Studies ........................................................................................................ 282
Chris L. Waller and Mary P. Bradley
QSAR Studies of Environmental Estrogens .......................................................................... 284
M. G. B. Drew, N. R. Price, and H. J. Wood
Quantitative Structure-Activity Relationship of Antimutagenic Benzalacetones and
Related Compounds ................................................................................................... 286
Chisako Yamagarni, Noriko Motohashi, and Miki Akamatsu
Multivariate Regression Excels Neural Networks, Genetic Algorithm and Partial
Least-Squares in QSAR Modeling ............................................................................ 288
Bono Lucie and Nenad Trinajstie
Structure-Activity Relationships of Nitrofuran Derivatives with Antibacterial Activity ...... 290
Jose Ricardo Pires, Astrea Giesbrecht, Suely L.Gomes, and Antonia T. do-Amaral
QSAR Approach for the Selection of Congeneric Compounds with Similar Toxicological
Modes of Action ....................................................................................................... 292
Paola Gramatica, Federica Consolaro, Marco Vighi, Roberto Todeschini,
Antonio Finizio, and Michael Faust
Strategies for Selection of Test Compounds in Structure-Affinity Modelling of Active
Carbon Adsorption Performance: A Multivariate Approach ..................................... 293
L.-G. HammarstrOm, 1. Fiingmark, P. G. J6nsson, P. R. Norman, A. L. Ness,
S. L. McFarlane, and N. M. Osmond
Design and QSAR of Dihydropyrazolo[4,3-cJQuinolinones as PDE4 Inhibitors ................. 295
M. L6pez, V. Segarra, M. 1. Crespo, J. Gracia, T. Domenech, J. Beleta, H. Ryder,
and J. M. Palacios
QSAR Based on Biological Microcalorimetry: On the Study of the Interaction between
Hydrazides and Escherichia coli and Saccharomyces cerevisiae .............................. 297
Maria Luiza Cruzera Montanari, Anthony Beezer, and Carlos Alberto Montanari
Cinnoline Analogs of Quinolones: Structural Consequences of the N Atom Introduction
in the Position 2 ......................................................................................................... 299
Marek L. Gl6wka, Dariusz Martynowski, Andrzej Olczak, and Alina Staszewska
x

3D Qllantitative Structure-Activity Relationship (CoMPA ) Study of Heterocyclic
Arylpiperazine Derivatives with 5-HT'A Activity ...................................................... 338
I1dik6 Magd6, Istvan Laszlovszky, Tibor Acs, and Gyorgy Domiiny
Molecular Similarity Analysis and 3D-QSAR of Neonicotinoid Insecticides ...............· . ...... 340
Masayuki Sukekawa and Akira Nakayama
3D-SAR Studies on a Series of Sulfonate Dyes as Protection Agents against j3-amyloid
Induced in Vitro Neurotoxicity ................................................................................. .342.
M. G. Cima, G. Gallo, M. Mabilia, M. O. Tinti, M. Castorina, C. Pisano,
and E. Tassoni
A New Molecular Structure Representation: Spectral Weighted Molecular (SWM)
Signals and Spectral Weighted Invariant Molecular (SWIM) Descriptors ............... .344
Roberto Todeschini, Viviana Consonni, David Galvagni, and Paola Gramatica
3D QSAR ofPmlyl4-Hydroxylase Inhibitors ..................................................................... .345
K.-H. Baringhaus, V. Guenzler-Pukall, G. Schubert, and K. Weidmann
Aromatase Inhibitors: Comparison between a CoMPA Model and the Enzyme Active
Site ............................................................................................................................ .347
Andrea Cavalli, Maurizio Recanatini, Giovanni Greco, and Ettore NoveIlino
Imidazoline Receptor Ligands-Molecular Modeling and 3D-QSAR CoMFA .................. .349
C. Marot, N. Baurin, J. Y. Merour, G. Guillaumet, P. Renard, and L. Morin-Allory
Poster Session III: Prediction of Ligand-Protein Binding
Reversible Inhibition of MAO-A and B by Diazoheterocyclic Compounds: Development
of QSARlCoMFA Models ........................................................................................ .353
Cosimo D. Altomare, Antonio Carrieri, Saverio Cellamare, Luciana Summo,
Angelo Carotti, Pierre-Alain Carrupt, and Bernard Testa
Modelling of the 5-Hf Receptor and Its Ligand Complexes .............................................. 355
2A
Estrella Lozoya, Maria Isabel Loza, and Ferran Sanz
Towards the Understanding of Species Selectivity and Resistance of Antimalarial DHFR
Inhibitors ......................................................................................... : .......................... 357
Thomas Lemcke, Inge Th!llger Christensen, and Flemming Steen J!Ilrgensen
Modeling of Suramin-TNFa Interactions ............................................................................. .359
Carola Marani Toro, Massimo Mabilia, Francesca Mancini, Marilena Giannangeli,
and Claudio Milanese
De Novo Design of Inhibitors of Protein Tyrosine Kinase pp60c-"" ...................................... .361
T. Langer, M. A. Konig, G. Schischkow, and S. Guccione
Elucidation of Active Conformations of Drugs Using Conformer Sampling by Molecular
Dynamics Calculations and Molecular Overlay ........................................................ 363
Shuichi Hirono and Kazuhiko Iwase
Differences in Agonist Binding Pattern for the GABA and the AMPA Receptors
A
Illustrated by High-Level ab Initio Calculations ...................................................... .365
Lena Tagmose, Lene Merete Hansen, Per-Ola Norrby, and Tommy Liljefors
Stabilization of the Ammonium-Carboxylate lon-Pair by an Aromatic Ring ...................... .367
Tommy Liljefors and Per-Ola Norrby
xii