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Drug Discovery Experience : Practices, Processes, and Perspectives,9780470942352
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Drug Discovery Experience : Practices, Processes, and Perspectives

by ;
Edition:
1st
ISBN13:

9780470942352

ISBN10:
0470942355
Format:
Hardcover
Pub. Date:
4/1/2013
Publisher(s):
Wiley
List Price: $125.00

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Summary

Edited by two distinguished chemists from academia and industry, this book presents an up-to-date overview of major aspects of drug discovery. It covers all ends of the discovery process from target selection to major therapeutic areas. Encompassing historical information, current methods, and future prospects, the coverage addresses novice medicinal chemists, providing them with a jump-start to their understanding of drug discovery. The perspectives on drug discovery, authored by experts in different fields and using case studies, also offer benefits to veteran medicinal and process chemists.

Author Biography

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.

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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