The Organic Chemistry of Drug Design and Drug Action, Fourth Edition presents a unique approach to medicinal chemistry based on physical organic chemical principles and reaction mechanisms that rationalize drug action. The book's coverage allows readers to extrapolate core principles and mechanisms to many related classes of drug molecules. It reflects the significant changes in the process of drug design over the last decade and preserves the successful approach of the previous editions while also including significant changes in format and coverage.
It is designed for undergraduate and graduate students in chemistry who are studying medicinal chemistry or pharmaceutical chemistry. Users, including research chemists and biochemists working in pharmaceutical and biotechnology industries will find this update to be useful in their daily work.
1. Chapter 1. Introduction - p. 1 2. Chapter 2. Lead Discovery - p. 21 3. 2.1 General considerations - p. 21 4. 2.2 Sources of lead compounds - p. 21 5. 2.3 Learning points - p. 59 6. 2.4 Check your learning - p. 60 7. 2.5 Practice problems - p. 60 8. Chapter 3. Lead Modification - p. 73 9. 3.1 Identification of the pharmacophore - p. 73 10. 3.2 Functional group modification - p. 75 11. 3.3 Structure–activity relationship - p. 76 12. 3.4 Structure modification to increase potency, therapeutic index, and ADME properties - p. 78 13. 3.5 Structure modifications to increase oral bioavailability and membrane permeability - p. 92 14. 3.6 Computational methods in lead modification - p. 104 15. 3.7 Epilogue - p. 118 16. 3.8 Practice problems - p. 119 17. Chapter 4. Proteins and Introduction to Receptors - p. 137 18. Chapter 5. Drug-Receptor Interactions - p. 159 19. 5.1 Introduction and general considerations - p. 159 20. 5.2 Important interactions (forces) involved in the drug-receptor complex - p. 160 21. 5.3 Determination of drug-receptor interactions - p. 166 22. 5.4 Theories of drug-receptor interactions - p. 171 23. 5.5 Topographical and stereochemical considerations - p. 175 24. 5.6 Case history of the pharmacodynamically-driven design of a receptor antagonist: cimetidine - p. 190 25. 5.7 Case history of the pharmacokinetically-driven design of a receptor antagonist: suvorexant - p. 195 26. 5.8 Case history of the design of receptor agonists: liraglutide and semaglutide - p. 198 27. 5.9 Practice problems - p. 199 28. CHAPTER 6. Enzymes - p. 207 29. Chapter 7. Enzyme Inhibition and Inactivation - p. 249 30. 7.1 Why inhibit an enzyme? - p. 249 31. 7.2 Reversible enzyme inhibitors - p. 252 32. 7.3 Irreversible enzyme inhibitors - p. 283 33. 7.4 PROTACs and molecular glues - p. 304 34. 7.5 Practice problems - p. 309 35. Chapter 8. Nucleic Acids - p. 325 36. Chapter 9. Drugs Interacting with Nucleic Acids - p. 343 37. 9.1 Introduction - p. 343 38. 9.2 Classes of drugs that interact with DNA - p. 345 39. 9.3 Drugs that interact with RNA and RNA-based drugs - p. 375 40. 9.4 Practice problems - p. 383 41. Chapter 10. Protein–Protein Interactions: Emerging Drug Targets - p. 397 42. Chapter 11. Drug Metabolism - p. 429 43. 11.1 Introduction - p. 429 44. 11.2 Synthesis of radioactive compounds - p. 431 45. 11.3 Analytical methods in drug metabolism - p. 434 46. 11.4 Pathways for drug deactivation and elimination - p. 437 47. 11.5 Practice problems - p. 479 48. Chapter 12. Drug Resistance and Drug Synergism - p. 495 49. Chapter 13. Prodrugs and Drug Delivery Systems - p. 525 50. 13.1 Introduction to prodrugs - p. 525 51. 13.2 Different types of prodrugs - p. 527 52. 13.3 Practice problems - p. 565 53. Appendix 1 - p. 579 54. Drugs Discovered Without Rational Design - p. 579 55. Drugs Discovered Without Rational Design - p. 580 56. Overview of Modern Rational Drug Design - p. 581 57. Overview of Modern Rational Drug Design - p. 584 58. General Consideration and Sources of Lead Compounds - p. 585 59. Identification of the Pharmacophore - p. 586 60. Identification of the Pharmacophore - p. 587 61. Functional Group Modification - p. 587 62. Functional Group Modification - p. 588 63. Structure–Activity Relationships (SARs) - p. 588 64. Structure–Activity Relationships (SARs) - p. 589 65. Structure Modification to Increase Potency, Therapeutic Index, and ADME Properties - p. 590 66. Structure Modification to Increase Potency, Therapeutic Index, and ADME Properties - p. 592 67. Structure Modifications to Increase Oral Bioavailability and Membrane Permeability - p. 593 68. Structure Modifications to Increase Oral Bioavailability and Membrane Permeability - p. 596 69. Computational Methods in Lead Modification - p. 597 70. Computational Methods in Lead Modification - p. 599 71. Enzymes as Catalysts - p. 600 72. Enzymes as Catalysts - p. 600 73. Mechanisms of Enzyme Catalysis - p. 601 74. Mechanisms of Enzyme Catalysis - p. 602 75. Coenzyme Catalysis - p. 603 76. Coenzyme Catalysis - p. 604 77. Enzyme Catalysis in Drug Discovery - p. 605 78. Enzyme Catalysis in Drug Discovery - p. 606 79. Why Inhibit an Enzyme? - p. 606 80. Why Inhibit an Enzyme? - p. 607 81. Reversible Enzyme Inhibitors - p. 607 82. Reversible Enzyme Inhibitors - p. 610 83. Irreversible Enzyme Inhibitors - p. 611 84. Irreversible Enzyme Inhibitors - p. 615 85. Proteolysis-Targeting Chimeras (PROTACs) and Molecular Glues - p. 616 86. Proteolysis-Targeting Chimeras (PROTACs) and Molecular Glues - p. 617 87. Drugs Targeting Protein–Protein Interactions - p. 618 88. Drugs Targeting Protein–Protein Interactions - p. 621 89. Other Drugs That Function by Targeting Protein–Protein Interaction - p. 622 90. Other Drugs That Function by Targeting Protein–Protein Interaction - p. 623 91. Introduction - p. 623 92. Introduction - p. 624 93. Synthesis of Radioactive Compounds - p. 625 94. Synthesis of Radioactive Compounds - p. 625 95. Analytical Methods in Drug Metabolism - p. 626 96. Analytical Methods in Drug Metabolism - p. 626 97. Pathways for Drug Deactivation and Elimination - p. 627 98. Pathways for Drug Deactivation and Elimination - p. 630 99. Introduction to Prodrugs - p. 631 100. Introduction to Prodrugs - p. 633 101. Carrier-linked Prodrugs - p. 633 102. Carrier-linked Prodrugs - p. 637 103. Bioprecursor Prodrugs - p. 638 104. Bioprecursor Prodrugs - p. 642 105. Appendix 2. Answers to Chapter Problems - p. 643 106. Index - p. 705
The Organic Chemistry of Drug Design and Drug Action, Fourth Edition presents a unique approach to medicinal chemistry based on physical organic chemical principles and reaction mechanisms that rationalize drug action. The book's coverage allows readers to extrapolate core principles and mechanisms to many related classes of drug molecules. It reflects the significant changes in the process of drug design over the last decade and preserves the successful approach of the previous editions while also including significant changes in format and coverage.
It is designed for undergraduate and graduate students in chemistry who are studying medicinal chemistry or pharmaceutical chemistry. Users, including research chemists and biochemists working in pharmaceutical and biotechnology industries will find this update to be useful in their daily work.
1. Chapter 1. Introduction - p. 1 2. Chapter 2. Lead Discovery - p. 21 3. 2.1 General considerations - p. 21 4. 2.2 Sources of lead compounds - p. 21 5. 2.3 Learning points - p. 59 6. 2.4 Check your learning - p. 60 7. 2.5 Practice problems - p. 60 8. Chapter 3. Lead Modification - p. 73 9. 3.1 Identification of the pharmacophore - p. 73 10. 3.2 Functional group modification - p. 75 11. 3.3 Structure–activity relationship - p. 76 12. 3.4 Structure modification to increase potency, therapeutic index, and ADME properties - p. 78 13. 3.5 Structure modifications to increase oral bioavailability and membrane permeability - p. 92 14. 3.6 Computational methods in lead modification - p. 104 15. 3.7 Epilogue - p. 118 16. 3.8 Practice problems - p. 119 17. Chapter 4. Proteins and Introduction to Receptors - p. 137 18. Chapter 5. Drug-Receptor Interactions - p. 159 19. 5.1 Introduction and general considerations - p. 159 20. 5.2 Important interactions (forces) involved in the drug-receptor complex - p. 160 21. 5.3 Determination of drug-receptor interactions - p. 166 22. 5.4 Theories of drug-receptor interactions - p. 171 23. 5.5 Topographical and stereochemical considerations - p. 175 24. 5.6 Case history of the pharmacodynamically-driven design of a receptor antagonist: cimetidine - p. 190 25. 5.7 Case history of the pharmacokinetically-driven design of a receptor antagonist: suvorexant - p. 195 26. 5.8 Case history of the design of receptor agonists: liraglutide and semaglutide - p. 198 27. 5.9 Practice problems - p. 199 28. CHAPTER 6. Enzymes - p. 207 29. Chapter 7. Enzyme Inhibition and Inactivation - p. 249 30. 7.1 Why inhibit an enzyme? - p. 249 31. 7.2 Reversible enzyme inhibitors - p. 252 32. 7.3 Irreversible enzyme inhibitors - p. 283 33. 7.4 PROTACs and molecular glues - p. 304 34. 7.5 Practice problems - p. 309 35. Chapter 8. Nucleic Acids - p. 325 36. Chapter 9. Drugs Interacting with Nucleic Acids - p. 343 37. 9.1 Introduction - p. 343 38. 9.2 Classes of drugs that interact with DNA - p. 345 39. 9.3 Drugs that interact with RNA and RNA-based drugs - p. 375 40. 9.4 Practice problems - p. 383 41. Chapter 10. Protein–Protein Interactions: Emerging Drug Targets - p. 397 42. Chapter 11. Drug Metabolism - p. 429 43. 11.1 Introduction - p. 429 44. 11.2 Synthesis of radioactive compounds - p. 431 45. 11.3 Analytical methods in drug metabolism - p. 434 46. 11.4 Pathways for drug deactivation and elimination - p. 437 47. 11.5 Practice problems - p. 479 48. Chapter 12. Drug Resistance and Drug Synergism - p. 495 49. Chapter 13. Prodrugs and Drug Delivery Systems - p. 525 50. 13.1 Introduction to prodrugs - p. 525 51. 13.2 Different types of prodrugs - p. 527 52. 13.3 Practice problems - p. 565 53. Appendix 1 - p. 579 54. Drugs Discovered Without Rational Design - p. 579 55. Drugs Discovered Without Rational Design - p. 580 56. Overview of Modern Rational Drug Design - p. 581 57. Overview of Modern Rational Drug Design - p. 584 58. General Consideration and Sources of Lead Compounds - p. 585 59. Identification of the Pharmacophore - p. 586 60. Identification of the Pharmacophore - p. 587 61. Functional Group Modification - p. 587 62. Functional Group Modification - p. 588 63. Structure–Activity Relationships (SARs) - p. 588 64. Structure–Activity Relationships (SARs) - p. 589 65. Structure Modification to Increase Potency, Therapeutic Index, and ADME Properties - p. 590 66. Structure Modification to Increase Potency, Therapeutic Index, and ADME Properties - p. 592 67. Structure Modifications to Increase Oral Bioavailability and Membrane Permeability - p. 593 68. Structure Modifications to Increase Oral Bioavailability and Membrane Permeability - p. 596 69. Computational Methods in Lead Modification - p. 597 70. Computational Methods in Lead Modification - p. 599 71. Enzymes as Catalysts - p. 600 72. Enzymes as Catalysts - p. 600 73. Mechanisms of Enzyme Catalysis - p. 601 74. Mechanisms of Enzyme Catalysis - p. 602 75. Coenzyme Catalysis - p. 603 76. Coenzyme Catalysis - p. 604 77. Enzyme Catalysis in Drug Discovery - p. 605 78. Enzyme Catalysis in Drug Discovery - p. 606 79. Why Inhibit an Enzyme? - p. 606 80. Why Inhibit an Enzyme? - p. 607 81. Reversible Enzyme Inhibitors - p. 607 82. Reversible Enzyme Inhibitors - p. 610 83. Irreversible Enzyme Inhibitors - p. 611 84. Irreversible Enzyme Inhibitors - p. 615 85. Proteolysis-Targeting Chimeras (PROTACs) and Molecular Glues - p. 616 86. Proteolysis-Targeting Chimeras (PROTACs) and Molecular Glues - p. 617 87. Drugs Targeting Protein–Protein Interactions - p. 618 88. Drugs Targeting Protein–Protein Interactions - p. 621 89. Other Drugs That Function by Targeting Protein–Protein Interaction - p. 622 90. Other Drugs That Function by Targeting Protein–Protein Interaction - p. 623 91. Introduction - p. 623 92. Introduction - p. 624 93. Synthesis of Radioactive Compounds - p. 625 94. Synthesis of Radioactive Compounds - p. 625 95. Analytical Methods in Drug Metabolism - p. 626 96. Analytical Methods in Drug Metabolism - p. 626 97. Pathways for Drug Deactivation and Elimination - p. 627 98. Pathways for Drug Deactivation and Elimination - p. 630 99. Introduction to Prodrugs - p. 631 100. Introduction to Prodrugs - p. 633 101. Carrier-linked Prodrugs - p. 633 102. Carrier-linked Prodrugs - p. 637 103. Bioprecursor Prodrugs - p. 638 104. Bioprecursor Prodrugs - p. 642 105. Appendix 2. Answers to Chapter Problems - p. 643 106. Index - p. 705
