Ernst Schering Research Foundation Workshop 15 Computer Aided Drug Design in Industrial Research

Transcription

1 Ernst Schering Research Foundation Workshop 15 Computer Aided Drug Design in Industrial Research

2 Ernst Schering Research Foundation Workshop 15 Computer Aided Drug Design in Industrial Research E. C. Herrmann, R. Franke Editors With 51 Figures and 16 Tables Springer-Verlag Berlin Heidelberg GmbH

3 ISBN ISBN (ebook) DOI / elp data applied for This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag Berlin Heidelberg GmbH. Violations are liable for prosecution under the German Copyright Law. Springer-Verlag Berlin Heidelberg 1995 Originally published by Springer-Verlag Berlin Heidelberg New York in 1995 Softcover reprint of the hardcover 1 st edition 1995 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Typesetting: Data conversion by Springer-Verlag 21/ Printed on acid-free paper

4 Preface The Ernst Schering Research Foundation sponsored its 15th workshop in Berlin on October 19-21, Leading scientists from Europe and North America were invited to discuss computer-aided drug design in industrial research. Computer-aided drug design is a very exciting field and an intellectual challenge, like playing chess. But these reasons are no longer sufficient to justify using this method in industry, if they ever were. Fig. 1. The participants of the workshop

5 VI Preface Therefore, when we, together with Prof. Hoyer, started to think about this workshop, our intentions quickly became clear. We were not so much interested in the very latest developments of methods or in computer-aided drug design itself - enough conferences have dealt with these topics. However, we were very interested in the usefulness and limitations of computer-aided drug design in the industrial research process. A lot has changed in the pharmaceutical industry recently. These changes are gaining momentum, so it is the right time to think about the role of computer-aided drug design in this changing environment. Just to mention two of these changes: First, most of us are faced with severe cost reduction programs and computer-aided drug design has to be judged by its possible impact on the bottom line; second, the significance of research is changing. Competition between pharmaceutical companies is much more pronounced nowadays. This competition is global and, even more importantly, it is competition by innovation. The title of an article in a research management journal highlights this quite clearly: '''Innovate or die' is the first rule of international industrial competition" (de Pury 1994). The issues of cost reduction and competition by innovation formed the setting for our workshop, where we wanted to discuss the role of computer-aided drug design in the overall quest for a new drug, addressing topics such as how computer-aided drug design can be integrated in the overall research process to have the most impact, what computer-aided drug design can contribute and where the pitfalls are, and what factors favor or prohibit successful contributions from computer-aided drug design. The goals set for this workshop were very ambitous, but we got much more than we ever expected. Indeed, this is reflected in these proceedings. We gratefully acknowledge the contributions of the authors of the chapters in this book and the assistance provided by the Ernst Schering Research Foundation, in particular by Dr. Ursula-F. Habenicht. E. C. Herrmann R. Franke

6 Preface VII Reference de Pury D (1994) "Innovate or die" is the first rule of international industrial competition. Research Technology Management 37(5):9-11

7 Table of Contents Some Aspects of Computational Chemistry G.-A. Hoyer Computer-Aided Drug Design in Industrial Research A Management Perspective J. G. Topliss Reflections on Collaborations of a Computational Chemist with Medicinal Chemists and Other Scientists 1'. Connolly Martin Structure-Based Ligand Design K. Gubemator, C. Brager, D. Bur, D. M. Doran, P. R. Gerber, K. Miiller, and T. M. Schaumann Chances and Risks of Modeling in Industry H. Koppen The Advantages of Using Rational Drug Design in Modem Drug Discovery: How to Integrate Computer-Aided Drug Design and Modem Biotechnology U. Norinder Screening Three-Dimensional Databases for Lead Finding H. P. Weber III

8 x Table of Contents 8 Optimization of Peptide Leads and Molecular Modeling 1. L Fauchere Quantitative Structure-Activity Relationships and Crystallography in Industrial Drug Design H. Kubinyi The Role of Structure-Based Ligand Design in Industrial Pharmaceutical Research 1. P. Tollenaere Drug Design Methods in Real-Life Situations: Recent Examples and Future Opportunities R. M. Hyde Theoretical Chemistry as Part of the Interdisciplinary Approach to Rational Drug Design E. Eckle and N. Heinrich Computer-Aided Drug Design in Industry: A Summary of Perspectives R. Franke and E.G. Herrmann Subject Index Previous Volumes Published in this Series

9 List of Contributors C. Broger Preclinical Pharmaceutical Research, Computational and Structural D. Bur Preclinical Pharmaceutical Research, Computational and Structural D.M. Doran Preclinical Pharmaceutical Research, Computational and Structural E. Eckle Institute of Physical Chemistry, Schering AG, MtillerstraBe 178, Berlin, Germany J. L. Fauchere Institut de Recherches SERVIER, 11, rue des Moulineaux, Suresnes-Paris, France R. Franke Consulting in Drug Design GbR, Basdorf, Germany P. R. Gerber Preclinical Pharmaceutical Research, Computational and Structural

10 XII List of Contributors K. Gubernator Preclinical Phannaceutical Research, Computational and Structural N. Heinrich Institute of Physical Chemistry, Schering AG, MiillerstraBe 178, Berlin, Germany E. C. Herrmann Institute of Physical Chemistry, Schering AG, MiillerstraBe 178, Berlin, Germany G.-A. Hoyer Institute of Physical Chemistry, Schering AG, MiillerstraBe 178, Berlin, Germany R. M. Hyde Department of Physical Sciences, Wellcome Research Laboratories, Langley Court, Beckenharn, Kent BR3 3BS, UK H. Koppen Medicinal Chemistry Department, Boehringer Ingelheim KG, Ingelheim, Germany H. Kubinyi Drug Design, ZHB/w, A 30, BASF AG, Ludwigshafen, Germany Y. C. Martin Phannaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, USA K. Muller Preclinical Pharmaceutical Research, Computational and Structural U. Norinder Karo Bio AB, P.O.B. 4032, Huddinge, Sweden T.M. Schaumann Preclinical Phannaceutical Research, Computational and Structural

11 List of Contributors XIII 1. P. Tollenaere Theoretical Medical Chemistry, Janssen Research Foundation, 2340 Beerse, Belgium 1. C. Topliss Department of Medicinal Chemistry, College of Pharmacy, The University of Michigan, Ann Arbor, MI , USA H. P. Weber Sandoz Pharma AG, Preclinical Research, 4002 Basel, Switzerland