Anti-AIDS drug development : challenges, strategies and prospects

309 Pages·1995·94.208 MB·English

by  Mohan, Prem

ANTI-AIDS DRUG DEVELOPMENT
Challenges, Strategies and Prospects

ANTI-AIDS DRUG DEVELOPMENT
Challenges, Strategies and Prospects
Edited by
Prem Mohan
Formerly of the University of fllinois at Chicago, USA
and
Masanori Baba
Center for Chronic Viral Diseases, Kagoshima University, japan
Boca Raton London New York
CRC Press is an imprint of the
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First published 1995 by Harwood Academic Publishers
Published 2018 by CRC Press
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© 1995 by Taylor & Francis Group, LLC
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ISBN 13: 978-3-7186-5698-1 (hbk)
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British Library Cataloguing in Publication Data
Anti-AIDS Drug Development: Challenges
Strategies and Prospects
I. Mohan, Prem II. Baba, Masanori
616.9792061
CONTENTS
Preface vii
List of Contributors ix
1 From Anti-HIV Agents to Anti-AIDS Chemotherapy:
A Critical Appraisal 1
Erik De Clercq
2 Nucleosides and Derivatives 39
Lak S. Jeong, Hea O. Kim, J. Warren Beach, Won K Chung,
Moon W. Chun, and Chung K. Chu
3 Iminosugar a-Glucosidase Inhibitors 65
Gary S. Jacob and Martin L. Bryant
4 Inhibition of HIV Protease: A Strategy for the Treatment of AIDS 93
Joel R. Huff and Paul L. Darke
5 Regulatory Proteins of Human Immunodeficiency
Virus and Therapy 117
Takashi Okamoto
6 CD4 Mimetics and Analogs 129
Michael E. Johnson and Zhaolan Lin
7 Antisense Oligonucleotide Approach for Therapy of AIDS 143
Sudhir Agrawal
8 Resistance to Anti-HIV Agents for Anti-AIDS Drug Development 163
Douglas D. Richman
9 Anti-HIV Drug Test Systems: Significance and Limitations 185
Mark F. Kavlick and Hiroaki Mitsuya
10 Plant-derived Anti-HIV Agents 211
A. Douglas Kinghom
11 HIV-1-specific Reverse Transcriptase Inhibitors 239
Masanori Baba, Jan Balzarini, Rudi Pauwels and Erik De Clercq
12 Small and Large Polyanionic Derivatives 269
Prem Mohan
Index 291

PREFACE
It has been over a decade since human immunodeficiency virus (HIV) was
discovered as the causative agent of AIDS. In spite of a world-wide effort coupled
with an enormous investment in all aspects of AIDS research, HIV continues
to remain a formidable and as yet unsurpassed impediment to the antiviral
chemotherapy of AIDS. Developments in the molecular biology of HIV have
revealed that the virus is endowed with a complex genetic composition and
a molecular architecture that provides it with inherent and evolving mechanisms
for immune evasion and drug resistance. Such properties alone makes HIV the
most sought after drug target in the history of drug design research. In response
to this unprecedented challenge, researchers around the globe have mounted
a vigorous and tireless attack on a variety of potential drug targets.
This book aims to cover the major arenas of drug development that have
contributed to our better understanding of the pros and cons of the various
efforts of chemists and biologists. Clearly, there is more work to be done.
Biologists need to explore newer antiviral targets for HIV replication. Medicinal
chemists need to look for and design molecules that will remain highly potent
and selective, have minimal toxicities and be devoid of inducing resistance.
Considering the inability of currently used agents to cure AIDS, it may be that
we need a new paradigm in our search for potential agents. Compounds having
newer mechanisms of action should be explored if they have a reasonable
selectivity index. Existing derivatives that interact with known targets can also
be pursued, but they will need significant structural modifications to overcome
their limitations. In other words, we need to encourage all possible strategies
with the hope that these approaches will provide the needed curative recipe
to finally triumph over AIDS.

CONTRIBUTORS
Sudhir Agrawal, Moon W. Chun,
Hybridon, Inc., College of Pharmacy,
One Innovation Drive, Seoul National University,
Worcester, MA 01605, USA Seoul, Korea
Masanori Baba, Won K. Chung,
Division of Human Retroviruses, College of Pharmacy,
Center for Chronic Viral Diseases, Seoul National University,
Faculty of Medicine, Seoul, Korea
Kagoshima University,
Kagoshima 890, Japan Paul L. Darke,
Department of Biological Chemistry,
Jan Balzarini, Merck Research Laboratories,
Rega Institute for Medical Research, P. O. Box 4, WP26-410,
Katholieke Universiteit Leuven, West Point, Pennsylvania 19486,
Minderbroedersstraat 10, USA
B-3000 Leuven, Belgium
Joel R. Huff,
J. Warren Beach, Department of Medicinal Chemistry,
Department of Medicinal Chemistry, Merck Research Laboratories,
College of Pharmacy, P. O. Box 4, WP26-410,
The University of Georgia, West Point, Pennsylvania 19486,
Athens, GA 30602, USA USA
Martin L. Bryant, Gary S. Jacob,
Department of Infectious Diseases, Glycosciences Section,
G. D. Searle, 700 Chesterfield Department of Immunology,
Village Parkway, Monsanto Corporate Research,
St. Louis, Missouri 63198, USA 800 North Lindbergh Blvd.,
St. Louis, Missouri 63167,
Erik De Clercq, USA
Rega Institute for Medical Research,
Katholieke Universiteit Leuven, Lak S. Jeong
Minderbroedersstraat 10, Department of Medicinal Chemistry,
B-3000 Leuven, Belgium College of Pharmacy,
The University of Georgia,
Chung K. Chu, Athens, GA 30602,
Department of Medicinal Chemistry, USA
College of Pharmacy,
The University of Georgia,
Athens, GA 30602, USA