Table Of ContentSAR
Side Effects and Drug Design
MEDICINAL RESEARCH
A Series of Monographs
Editor
Gary L. Grunewald, University ofKansas
Editorial Advisory Board
John W. Daly, National Institutes of Health
Gertrude B. Elion, Wel/come Research Laboratories
Saul B. Kadin, Charles Pfizer and Co.
Yvonne C. Martin, Abbott Laboratories
Wendel L. Nelson, University of Washington
P. S. Portoghese, University of Minnesota
David J. Triggle, State University ofNew York at Buffalo
1. Drugs Affecting the Peripheral Nervous System
edited by Alfred Burger (out of print)
2. Drugs Affecting the Central Nervous System
edited by Alfred Burger (out of print)
3. Selected Pharmacological Testing Methods
edited by Alfred Burger (out ofprint)
4. Analytical Metabolic Chemistry of Drugs
edited by Jean L. Hirtz (out ofprint)
5. Biogenic Amines and Physiological Membranes in Drug Therapy
edited by John H. Biel and Leo G. A hood
6. Search for New Drugs
edited by Alan A. Rubin
7. Clofibrate and Related Analogs
by Donald T. Witiak, Howard A. I. Newman, and Dennis R. Feller
8. Quantitative Drug Design: A Critical Introduction
by Yvonne Connolly Martin
9. The Chemistry of the Tetracycline Antibiotics
by Lester A. Mitscher
I0. Physical Chemical Properties of Drugs
edited by Samuel H. Yalkowsky, A11tho11y A. Sinkula, a11d Shri C l'afra11i
11. SAR: Side Effects and Drug Design
by Eric J. Lien
Additional Volumes in Preparatio11
SAR
Side Effects and Drug Design
ERICJ. LIEN
University ofSouthern California
Los Angeles, California
0
CRC Press
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To my parents, W. S. Lien and Y . C . Lin Lien, for their
appreciation of the value of higher education
To my wife, Linda Lin-min, for her encouragement and un-
derstanding
To my sons, Raymond and Andrew , for letting me finish this
seemingly never-ending project
To my students, for letting me use them as the test subjects
of the materials presented
About the Series
This series of monographs was conceived by the late Dr. Fred
Schueler of Tulane University. His untimely death came prior to
the completion of the first volumes of the series, and his friend
and very able colleague, Dr. Alfred Burger of the University of
Virginia, took on the task of editing the first three volumes of
the series. Dr. Burger's heavy responsibilities forced him to
withdraw from further active participation with the series, and
the next three volumes were selected from books already under
contract to Marcel Dekker, Inc. , with Dr. Gary Grunewald of
the University of Kansas as Consulting Editor. At this point an
Editorial Advisory Board was selected and Grunewald became the
Series Editor. The traditions established under the leadership
of Schueler and Burger will be continued.
It is hoped that books for the series will serve a useful role
in the areas of medicinal chemistry, chemical pharmacology, and
biochemistry. It is the intent of the Editor and the Editorial Ad-
visory Board that books selected for the series should be timely
and fill a definite need in the general areas mentioned. We
welcome suggestions for future monographs in the series.
Gary L. Grunewald
V
Preface
This book is a combination of my research work in the area of
the quantitative structure-activity relationship of disposition and
activities of various pharmacological groups and a graduate course
on SAR and drug design I have taught over the last 15 years.
Also included is the first systematic attempt at linking side ef-
fects of drugs to their molecular structures and physicochemical
properties.
This monograph is intended for graduate students in medic-
inal chemistry, pharmaceutical chemistry, pharmacology, and
toxicology and for upper-class students in pharmacy, medicine,
veterinary medicine, and other health sciences who are interested
in learning about the strategy and problems associated with the
design and development of new drugs, as well as for industrial
research scientists in these fields.
No one has the gift of prophecy in designing new drugs,
but it would be a costly proposition not to be familiar with exist-
ing working models, their advantages and weaknesses, and many
reported cases of adverse reactions on clinically used drugs or
common chemicals. It has been estimated that it will cost about
$100 million to discover and market a new drug. It might cost
even more money to discontinue a new drug and to settle all
litigation, should the drug cause widespread serious problems,
not to mention unnecessary human suffering.
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