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The Drug Discovery Experience

Practices, Processes, and Perspectives

Erschienen am 26.04.2013, 1. Auflage 2013
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ISBN/EAN: 9780470942352
Sprache: Englisch
Umfang: 570 S.
Einband: gebundenes Buch

Beschreibung

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.

Autorenportrait

InhaltsangabeChapter 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. Antiinflammatory Drugs 26 8. Antiulcer 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. Antianginal 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. Antihistamines 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

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