Drug Discovery: Practices, Processes, and Perspectives

Overview

Sets forth the history, state of the science, and future directions of drug discovery

Edited by Jie Jack Li and Nobel laureate E. J. Corey, two leading pioneers in drug discovery and medicinal chemistry, this book synthesizes great moments in history, the current state of the science, and future directions of drug discovery into one expertly written and organized work. Exploring all major therapeutic areas, the book introduces readers to all facets and phases of drug discovery, ...

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Overview

Sets forth the history, state of the science, and future directions of drug discovery

Edited by Jie Jack Li and Nobel laureate E. J. Corey, two leading pioneers in drug discovery and medicinal chemistry, this book synthesizes great moments in history, the current state of the science, and future directions of drug discovery into one expertly written and organized work. Exploring all major therapeutic areas, the book introduces readers to all facets and phases of drug discovery, including target selection, biological testing, drug metabolism, and computer-assisted drug design.

Drug Discovery features chapters written by an international team of pharmaceutical and medicinal chemists. Contributions are based on a thorough review of the current literature as well as the authors' firsthand laboratory experience in drug discovery. The book begins with the history of drug discovery, describing groundbreaking moments in the field. Next, it covers such topics as:

  • Target identification and validation
  • Drug metabolism and pharmacokinetics
  • Central nervous system drugs
  • In vitro and in vivo assays
  • Cardiovascular drugs
  • Cancer drugs

Each chapter features a case study, helping readers understand how science is put into practice throughout all phases of drug discovery. References at the end of each chapter serve as a gateway to groundbreaking original research studies and reviews in the field.

Drug Discovery is ideal for newcomers to medicinal chemistry and drug discovery, providing a comprehensive overview of the field. Veterans in the field will also benefit from the perspectives of leading international experts in all aspects of drug discovery.

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Editorial Reviews

From the Publisher

“Taken together, the book is an excellent introduction into drug discovery and an eminent summary of the very important milestones of drug discovery in the most critical indication areas. This book is a valuable addition to the library of all different kinds of scientists working in the field of drug discovery.” (ChemMedChem, 1 October 2013)

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Product Details

  • ISBN-13: 9780470942352
  • Publisher: Wiley
  • Publication date: 4/1/2013
  • Edition number: 1
  • Pages: 570
  • Sales rank: 807,609
  • Product dimensions: 7.30 (w) x 10.00 (h) x 1.50 (d)

Meet the Author

JIE JACK LI, PhD, is a chemist at Bristol-Myers Squibb Company. He has authored or edited several books published by Wiley, including Name Reactions in Heterocyclic Chemistry, Name Reactions for Functional Group Transformations, Name Reactions for Homologations (Part I and Part II), Name Reactions for Carbocyclic Ring Formations, Contemporary Drug Synthesis, The Art of Drug Synthesis, and Modern Drug Synthesis.

E. J. COREY, PhD, has been a Professor at Harvard University since 1959. The 1990 Nobel Laureate in Chemistry, Dr. Corey has also been the recipient of more than seventy international awards and honorary degrees, including the U.S. National Medal of Science, the Japan Prize in Science, and the Priestley Medal. Author of more than 1,500 publications, he is one of the most cited authors in science.

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Table of Contents

Chapter 1. History of Drug Discovery 1

1. Introduction 1

2. Antibacterials 1

3. Cancer Drugs 6

4. Cardiovascular Drugs 10

5. Cholesterol Drugs 16

6. CNS Drugs 21

7. Anti-inflammatory Drugs 26

8. Anti-ulcer Drugs 30

9. Antiviral Drugs 33

10. References 38

Chapter 2. Target Identification and Validation 43

1. History 43

2. Definition of Drug Targets 43

3. Classification of Currently Utilized Drug Targets 45

4. Receptors as Drug Targets 46

5. Enzymes as Drug Targets 48

6. Transporter Proteins as Drug Targets 49

7. Modern Technologies Employed in Target Identification and Validation 49

8. Impact of Therapeutic Modalities on the Selection Drug Targets 62

9. Future Directions 63

10. References

3. In vitro and in vivo Assays 67

1. Introduction 67

2. The Testing Funnel 67

3. In vitro assays 70

4. In vivo Assays 89

5. Outlook 92

6. References 93

Chapter 4. Drug Metabolism and Pharmacokinetics in Drug Discovery 95

1. Introduction 95

2. Drug Metabolism 97

3. Pharmacokinetic Fundamentals 106

4. Drug Metabolism and Pharmacokinetics in Drug Discovery 95

1. Introduction 95

2. Drug Metabolism 97

3. Pharmacokinetic Fundamentals 106

4. Pharmacokinetics Studies in Support of Drug Optimization 112

5. Absorption and Permeability 114

6. Drug Transporters 117

7. Protein Binding 119

8. Pharmacokinetics and Pharmacodynamics 123

9. Predicting Human Pharmacokinetics 130

10. Summary 133

11. References 133

Chapter 5. Cardiovascular Drugs 137

1. Introduction 137

2. Early History of Coronary Heart Disease (CHD) 138

3. Lipid Lowering Agents 139

4. Antihypertensive Agents 153

5. Antithrombotic Drugs 177

6. Thrombolytic Agents 190

7. Anti-anginal Agents 191

8. Heart Failure Drugs 191

9. The Future 193

10. References 193

Chapter 6. Diabetes Drugs 201

1. Introduction 201

2. Current therapies for Type 2 Diabetes 204

3. Other Treatments for T2DM 215

4. Novel Mechanisms of Action: Future Treatments for Type 2 Diabetes 217

5. Current Therapies for Type 1 Diabetes 221

6. Future Treatments for Type 1 Diabetes 227

7. Future Prospects for New Diabetes Drugs 231

8. References 231

Chapter 7. CNS Drugs 241

1. Introduction 241

2. Antipsychotic Drugs 241

3. Antidepressant drugs 246

4. Drugs for Epilepsy and Bipolar Disorder 255

5. Anxiolytic Drugs 259

6. Centrally Acting Analgesic Drugs 262

7. Drugs for treating Substance Abuse and ADHD 265

8. Drugs for Neurodegenerative Diseases 267

9. Future Prospects for New CNS Drugs 273

10. References 276

Chapter 8. Cancer Drugs 283

1. Introduction 283

2. Historical Perspective of Cancer Drugs 285

3. Antimetabolites 286

4. Alkylating Agents 291

5. Platinum Complexes 294

6. Plant and Marine Based Natural Products 295

7. Toposiomerase Inhibitors 300

8. Antitumor Antibiotics 305

9. Tyrosine Kinase Inhibitors (TKI) 306

10. Hormones 314

11. Histone Deacylase (HDAC) Inhibitors 321

12. Miscellaneous Cancer Drugs 323

13. Conclusion 325

14. References 326

Chapter 9. Antiinflammatory and Immunomodulatory Drugs 333

1. Introduction 333

2. Arachidonic Acid Cascade 334

3. Leukotriene Pathway Inhibitors 347

4. Anti-histamines 351

5. Corticosteroids 353

6. Rheumatoid Arthritis 356

7. Osteoarthritis 363

8. Chronic Inflammatory Arthritis and Gout 364

9. Multiple Sclerosis 366

10. Transplantation 368

11. Biological Agents That Suppress Cytokine Production or Signaling 372

12. B Cell Therapy 374

13. Cytotoxic T-lymphocyte Antigen 4 (CTLA4) 374

14. Interleukins 375

15. Safety 377

16. Summary 377

17. References 378

Chapter 10. Anti-bacterial Drugs 385

1. Introduction 385

2. The Rise and Decline of Antibiotics 386

3. The Unique Challenges of Anti-bacterial Drug Discovery 387

4. Antibiotic Classes 390

5. Emerging Strategies to Discover New Anti-bacterial Drugs 420

6. Conclusions 425

7. References 425

Chapter 11. Antiviral Drug Discovery 437

1. Introduction 437

2. Human Immunodeficiency Virus-1 Inhibitors 442

3. Hepatitis B Virus Inhibitors 459

4. Hepatitis C Virus Inhibitors 463

5. Inhibitors of Respiratory Viruses-Influenza and Respiratory Syncytial Virus 476

6. Herpesviridae Inhibitors 487

7. Epilogue 490

8. References 490

Index 517

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