The Organic Chemistry of Drug Design and Drug Action

2nd Edition

Authors: Richard B. Silverman
Hardcover ISBN: 9780126437324
eBook ISBN: 9780080513379
Imprint: Academic Press
Published Date: 2nd December 2012
Page Count: 617
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Standard medicinal chemistry courses and texts are organized by classes of drugs with an emphasis on descriptions of their biological and pharmacological effects. This book represents a new approach based on physical organic chemical principles and reaction mechanisms that allow the reader to extrapolate to many related classes of drug molecules. The Second Edition reflects the significant changes in the drug industry over the past decade, and includes chapter problems and other elements that make the book more useful for course instruction.

Key Features

  • New edition includes new chapter problems and exercises to help students learn, plus extensive references and illustrations
  • Clearly presents an organic chemist's perspective of how drugs are designed and function, incorporating the extensive changes in the drug industry over the past ten years
  • Well-respected author has published over 200 articles, earned 21 patents, and invented a drug that is under consideration for commercialization


Advanced undergraduate and graduate students in organic-bioorganic and medicinal chemistry. Synthetic organic chemists. Practicing chemists in these fields working in the area of drug discovery and development

Table of Contents

I. Medicinal Chemistry Folklore
II. Discovery of New Drugs
General References
Drug Discovery, Design, and Development
I. Drug Discovery
A. Drug Discovery Without a Lead
1. Penicillins
2. Librium
B. Lead Discovery
1. Random Screening
2. Non-Random Screening
3. Drug Metabolism Studies
4. Clinical Observations
5. Rational Approaches to Lead Discovery
II. Lead Modification: Drug Design And Development
A. Identification of the Active Part: The Pharmacophore
B. Functional Group Modification
C. Structure-Activity Relationships (SAR)
D. Privileged Structures and Drug-Like Molecules
E. Structure Modification to Increase Potency and Therapeutic Index
1. Homologation
2. Chain Branching
3. Ring-chain Transformations
4. Bioisosterism
5. Combinatorial Chemistry
a. General Aspects
b. Split synthesis: peptide libraries
c. Encoding combinatorial libraries
d. Nonpeptide libraries
6. SAR by NMR/ SAR by MS
7. Peptidomimetics
F. Structure Modifications to Increase Oral Bioavailability
1. Electronic Effects: The Hammett Equation
2. Lipophilicity Effects
a. Importance of Lipophilicity
b. Measurement of Lipophilicities
c. Computerization of log P Values
d. Membrane Lipophilicity
3. Effects of Ionization on Lipophilicity and Oral Bioavailability
4. Other P


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© Academic Press 2004
Academic Press
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About the Author

Richard B. Silverman

Professor Richard B. Silverman received his B.S. degree in chemistry from The Pennsylvania State University in 1968 and his Ph.D. degree in organic chemistry from Harvard University in 1974 (with time off for a two-year military obligation from 1969-1971). After two years as a NIH postdoctoral fellow in the laboratory of the late Professor Robert Abeles in the Graduate Department of Biochemistry at Brandeis University, he joined the chemistry faculty at Northwestern University. In 1986, he became Professor of Chemistry and Professor of Biochemistry, Molecular Biology, and Cell Biology. In 2001, he became the Charles Deering McCormick Professor of Teaching Excellence for three years, and since 2004 he has been the John Evans Professor of Chemistry. His research can be summarized as investigations of the molecular mechanisms of action, rational design, and syntheses of potential medicinal agents acting on enzymes and receptors. His awards include DuPont Young Faculty Fellow (1976), Alfred P. Sloan Research Fellow (1981-1985), NIH Research Career Development Award (1982-1987), Fellow of the American Institute of Chemists (1985), Fellow of the American Association for the Advancement of Science (1990), Arthur C. Cope Senior Scholar Award of the American Chemical Society (2003), Alumni Fellow Award from Pennsylvania State University (2008), Medicinal Chemistry Hall of Fame of the American Chemical Society (2009), the Perkin Medal from the Society of Chemical Industry (2009), the Hall of Fame of Central High School of Philadelphia (2011), the E.B. Hershberg Award for Important Discoveries in Medicinally Active Substances from the American Chemical Society (2011), Fellow of the American Chemical Society (2011), Sato Memorial International Award of the Pharmaceutical Society of Japan (2012), Roland T. Lakey Award of Wayne State University (2013), BMS-Edward E. Smissman Award of the American Chemical Society (2013), the Centenary Prize of the Royal Society of Chemistry (2

Affiliations and Expertise

Northwestern University, Evanston, IL, USA


"...this text is directed towards graduates who are embarking on a career in medicinal chemistry in the discovery laboratory. Sliverman continues to blur the edges between chemistry and pharmacology in a manner that is incontrovertibly relevant to the discipline of drug design and development." --Michael E. Cooper, GE Healthcare, The Maynard Centre, in DDT, VOL. 9, 2004

"What stands out in comparison with other books discussed here is that the subjects are generally addressed in detail, and each theoretical point is illustrated with examples of specific drugs. A great deal of knowledge is reflected...that is suitable for both advanced students and PhDs a like who have not yet become acquainted with the area, but who wish to prepare themselves for a career in drug research." --ORGANIC CHEMISTRY ORG., 2005

Praise for the First Edition:
"This book is a tour de force in the title area...This book would be appropriate for advanced undergraduate students and graduate students...strongly recommended to scientists who are seeking an efficient introduction to medicinal chemistry, background in a specific drug principle or category, or a dose of inspiration." --JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

"... unified, well-organized and clearly presented ...It is so clearly written that it will be of value to both students and veteran scientists...My congratulations to Dr. Silverman in consolidating such a multiplicity of facts and data so as to truly begin to reduce medicinal chemistry from a hybrid of chemistry, pharmacology and related sciences to a single, clearly defined, rationalized discipline." --Carl Kaiser, Director of Medicinal Chemistry, NOVA PHARMACEUTICAL CORPORATION

"The author shows an uncanny ability to present the salient principles in a systematic, well-balanced and logical way..." --William C. Groutas, WICHITA STATE UNIVERSITY