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.‎ New to this edition‎:‎ * 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-‎?‎ 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