The Organic Chemistry of Drug Design and Drug Action

3rd Edition

Authors: Richard B. Silverman Mark W. Holladay
Hardcover ISBN: 9780123820303
eBook ISBN: 9780123820310
Imprint: Academic Press
Published Date: 21st May 2014
Page Count: 536
Tax/VAT will be calculated at check-out
Compatible Not compatible
VitalSource PC, Mac, iPhone & iPad Amazon Kindle eReader
ePub & PDF Apple & PC desktop. Mobile devices (Apple & Android) Amazon Kindle eReader
Mobi Amazon Kindle eReader Anything else

Institutional Access


The Organic Chemistry of Drug Design and Drug Action, Third Edition, represents a unique approach to medicinal chemistry based on physical organic chemical principles and reaction mechanisms that rationalize drug action, which allows the reader to extrapolate those core principles and mechanisms to many related classes of drug molecules. This new edition reflects significant changes in the process of drug design over the last decade. It preserves the successful approach of the previous editions while including significant changes in format and coverage.

Key Features

  • Updates to all chapters, including new examples and references
  • Chapter 1 (Introduction): Completely rewritten and expanded as an overview of topics discussed in detail throughout the book
  • Chapter 2 (Lead Discovery and Lead Modification): Sections on sources of compounds for screening including library collections, virtual screening, and computational methods, as well as hit-to-lead and scaffold hopping; expanded sections on sources of lead compounds, fragment-based lead discovery, and molecular graphics; and deemphasized solid-phase synthesis and combinatorial chemistry
  • Chapter 3 (Receptors): Drug-receptor interactions, cation-π and halogen bonding; atropisomers; case history of the insomnia drug suvorexant
  • Chapter 4 (Enzymes): Expanded sections on enzyme catalysis in drug discovery and enzyme synthesis
  • Chapter 5 (Enzyme Inhibition and Inactivation): New case histories:
    • for competitive inhibition, the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib and Abelson kinase inhibitor, imatinib
    • for transition state analogue inhibition, the purine nucleoside phosphorylase inhibitors, forodesine and DADMe-ImmH, as well as the mechanism of the multisubstrate analog inhibitor isoniazid
    • for slow, tight-binding inhibition, the dipeptidyl peptidase-4 inhibitor, saxagliptin
  • Chapter 7 (Drug Resistance and Drug Synergism): This new chapter includes topics taken from two chapters in the previous edition, with many new examples
  • Chapter 8 (Drug Metabolism): Discussions of toxicophores and reactive metabolites
  • Chapter 9 (Prodrugs and Drug Delivery Systems): Discussion of antibody–drug conjugates


Undergraduate and graduate students in chemistry studying medicinal chemistry or pharmaceutical chemistry; research chemists and biochemists working in pharmaceutical and biotechnology industries

Table of Contents

  • Dedications
  • Preface to the First Edition
  • Preface to the Second Edition
  • Preface to the Third Edition
  • Chapter 1. Introduction
    • 1.1. Overview
    • 1.2. Drugs Discovered without Rational Design
    • 1.3. Overview of Modern Rational Drug Design
    • 1.4. Epilogue
    • 1.5. General References
    • 1.6. Problems (Answers can be found in the Appendix at the end of the book)
  • Chapter 2. Lead Discovery and Lead Modification
    • 2.1. Lead Discovery
    • 2.2. Lead Modification
    • 2.3. General References
    • 2.4. Problems (Answers Can be Found in the Appendix at the End of the Book)
  • Chapter 3. Receptors
    • 3.1. Introduction
    • 3.2. Drug–Receptor Interactions
    • 3.3. General References
    • 3.4. Problems (Answers can be Found in the Appendix at the End of the Book)
  • Chapter 4. Enzymes
    • 4.1. Enzymes as Catalysts
    • 4.2. Mechanisms of Enzyme Catalysis
    • 4.3. Coenzyme Catalysis
    • 4.4. Enzyme Catalysis in Drug Discovery
    • 4.5. General References
    • 4.6. Problems (Answers can be Found in the Appendix at the End of the Book)
  • Chapter 5. Enzyme Inhibition and Inactivation
    • 5.1. Why Inhibit an Enzyme?
    • 5.2. Reversible Enzyme Inhibitors
    • 5.3. Irreversible Enzyme Inhibitors
    • 5.4. General References
    • 5.5. Problems (Answers can be Found in the Appendix at the End of the Book)
  • Chapter 6. DNA-Interactive Agents
    • 6.1. Introduction
    • 6.2. DNA Structure and Properties
    • 6.3. Classes of Drugs that Interact with DNA
    • 6.4. General References
    • 6.5. Problems (Answers Can be Found in the Appendix at the End of the Book)
  • Chapter 7. Drug Resistance and Drug Synergism
    • 7.1. Drug Resistance
    • 7.2. Drug Synergism (Drug Combination)</l


No. of pages:
© Academic Press 2015
Academic Press
eBook ISBN:
Hardcover ISBN:

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

Mark W. Holladay

Dr. Mark W. Holladay is Vice President of Drug Discovery and Medicinal Chemistry at Ambit Biosciences (San Diego, California) where he leads drug discovery programs in oncology and autoimmune diseases and has contributed to compounds in clinical development. He began his drug hunting career at Abbott Laboratories where he achieved the position of Volwiler Associate Research Fellow as a medicinal chemist and project leader in the Neurosciences Research Area. He also conducted collaborative drug discovery research as a member of contract research organizations including Biofocus and Discovery Partners International. He is a co-author on over 70 peer-reviewed research articles, reviews, or chapters and is named as an inventor on over 40 patents and patent applications. Dr. Holladay earned his undergraduate degree from Vanderbilt University, his Ph.D. at Northwestern University under the direction of Professor Richard B. Silverman, and conducted postdoctoral studies with Professor Daniel H. Rich at the University of Wisconsin-Madison.

Affiliations and Expertise

Ambit Biosciences, San Diego, CA, USA