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)


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

About the author

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