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Modern Drug Synthesis: (Wiley Series on Drug Synthesis)

Modern Drug Synthesis: (Wiley Series on Drug Synthesis)

          
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About the Book

Following Contemporary Drug Synthesis and The Art of Drug Synthesis (Wiley, 2004 and 2007), two well-received works, is this new book that demystifies the process of modern drug discovery for practitioners and students. An enhanced introduction covers areas such as background, pharmacology, SAR, PK/PD, efficacy, and safety. Focusing on the advantages of process synthesis versus the discovery synthetic route, Modern Drug Synthesis features authoritative coverage by distinguished editors and authors (some chapter authors are the actual inventor of the drug) of twenty different drug molecules.

Table of Contents:
Preface xi Contributors xiii I. Infectious Diseases 1 Chapter 1. Raltegravir (Isentress), The First-in-class HIV-1 Integrase Inhibitor 3 Julianne A. Hunt 1.1 Background 3 1.2 Pharmacology 5 1.3 Structure-Activity Relationship (SAR) 6 1.4 Pharmacokinetics and Drug Metabolism 8 1.5 Efficacy and Safety 9 1.6 Syntheses 10 1.7 References 13 Chapter 2. Maraviroc (Selzentry), The First-in-class CCR5 Antagonist for the Treatment of HIV 17 David Price 2.1 Background 17 2.2 Structure-Activity Relationship (SAR) 19 2.3 Pharmacokinetics and Safety 21 2.4 Syntheses 22 2.5 References 27 Chapter 3. Darunavir (Prezista), A HIV-1 Protease Inhibitor for Treatment of Multidrug Resistant HIV 29 Arun K. Ghosh and Cuthbert D. Martyr 3.1 Background 29 3.2 Pharmacology 32 3.3 Structure-Activity Relationship (SAR) 32 3.4 Pharmacokinetics and Drug Metabolism 33 3.5 Efficacy and Safety 33 3.6 Syntheses 34 3.7 References 42 II. Cancer 45 Chapter 4. Decitabine (Dacogen), A DNA Methyltransferase Inhibitor for Cancer 47 Jennifer A. Van Camp 4.1 Background 47 4.2 Pharmacology 49 4.3 Structure-Activity Relationship (SAR) 49 4.4 Pharmacokinetics and Drug Metabolism 50 4.5 Efficacy and Safety 50 4.6 Syntheses 51 4.7 References 54 Chapter 5. Capecitabine (Xeloda), An Oral Chemotherapy Agent 57 R. Jason Herr 5.1 Background 57 5.2 Pharmacology 60 5.3 Structure-Activity Relationship (SAR) 62 5.4 Pharmacokinetics and Efficacy 63 5.5 Syntheses 64 5.6 References 70 Chapter 6. Sorafenib (Nexavar), A Multi-kinase Inhibitor for Advanced Renal Cell Carcinoma and Unresectable Hepatocellular Carcinoma 73 Shuanghua Hu 6.1 Background 73 6.2 Pharmacology 75 6.3 Structure-Activity Relationship (SAR) 77 6.4 Pharmacokinetics and Drug Metabolism 78 6.5 Efficacy and Safety 78 6.6 Syntheses 79 6.7 References 84 Chapter 7. Sunitinib (Sutent), An Angiogenesis Inhibitor 87 Martin Pettersson 7.1 Background 87 7.2 Discovery and Development 89 7.3 Syntheses 91 7.3.1 Discovery Route 91 7.3.2 Process Route 92 7.4 References 97 Chapter 8. Bortezomib (Velcade), A First-in-class Proteasome Inhibitor 99 Benjamin S. Greener and David S. Millan 8.1 Background 99 8.2 Pharmacology 101 8.3 Structure-Activity Relationship (SAR) 102 8.4 Pharmacokinetics and Drug Metabolism 104 8.5 Efficacy and Safety 104 8.6 Syntheses 105 8.7 References 109 Chapter 9. Pazopanib (Votrient), A VEGFR Tyrosine Kinase Inhibitor for Cancer 111 Ji Zhang and Jie Jack Li 9.1 Background 111 9.2 Pharmacology 113 9.3 Structure?Activity Relationship (SAR) 114 9.4 Pharmacokinetics and Drug Metabolism 117 9.5 Efficacy and Safety 118 9.6 Syntheses 118 9.7 Other VEGFR Inhibitors in Development: Vandetanib and Cediranib 120 9.8 References 121 III. Cardiovascular and Metabolic Diseases 123 Chapter 10. Sitagliptin (Januvia), A Treatment for Type 2 Diabetes 125 Scott D. Edmondson, Feng Xu, and Joseph D. Armstrong III 10.1 Background 125 10.2 Pharmacology 126 10.3 Structure-Activity Relationship (SAR) 127 10.4 Pharmacokinetics and Drug Metabolism 128 10.5 Efficacy and Safety 129 10.6 Syntheses 130 10.7 References 138 Chapter 11. Aliskiren (Tekturna), The First-in-class Renin Inhibitor for Hypertension 141 Victor J. Cee 11.1 Background 141 11.2 Pharmacology 144 11.3 Structure-Activity Relationship (SAR) n145 11.4 Pharmacokinetics and Drug Metabolism 146 11.5 Efficacy and Safety 147 11.6 Syntheses 148 11.7 References 156 Chapter 12. Vernakalant (Kynapid), An Investigational Drug for the Treatment of Atrial Fibrillation 159 David L. Gray 12.1 Background 159 12.2 Pharmacology 163 12.3 Structure-Activity Relationship (SAR) 163 12.4 Pharmacokinetics and Drug Metabolism 164 12.5 Efficacy and Safety 165 12.6 Syntheses 166 12.7 References 171 Chapter 13. Conivaptan (Vaprisol), Vasopressin V1a and V2 Antagonist for Hyponatremia 175 Brian A. Lanman 13.1 Background 175 13.2 Pharmacology 177 13.3 Structure-Activity Relationship (SAR) 179 13.4 Pharmacokinetics and Drug Metabolism 181 13.5 Efficacy and Safety 182 13.6 Syntheses 183 13.7 References 189 Chapter 14. Rivaroxaban (Xarelto), A Factor Xa Inhibitor for the Treatment of Thrombotic Events 191 Ji Zhang and Jason Crawford 14.1 Background 191 14.2 Pharmacology 193 14.3 Structure?Activity Relationship (SAR) 194 14.4 Pharmacokinetics and Drug Metabolism 196 14.5 Efficacy and Safety 197 14.6 Syntheses 198 14.7 Compounds in Development: Apixaban and Otamixaban 203 14.8 References 204 Chapter 15. Endothelin Antagonists for the Treatment of Pulmonary Arterial Hypertension 207 David Edmonds 15.1 Background 208 15.2 Treatment of PAH 209 15.3 Endothelin Antagonists 211 15.4 Synthesis of Bosentan 215 15.5 Synthesis of Sitaxsentan 217 15.6 Synthesis of Ambrisentan 219 15.7 Conclusion 221 15.8 References 221 IV. Central Nervous System Diseases 225 Chapter 16. Varenicline (Chantix), An α4β2 Nicotinic Receptor Partial Agonist for Smoking Cessation 227 Jotham W. Coe, Frank R. Busch and Robert A. Singer 16.1 Background 227 16.2 Discovery Chemistry Program 229 16.3 Pharmacology 231 16.4 Pharmacokinetics and Drug Metabolism 231 16.5 Efficacy and Safety 232 16.6 Syntheses 232 16.7 References 244 Chapter 17. Donepezil, Rivastigmine, Galantamine: Cholinesterase Inhibitors for Alzheimer's Disease 249 Subas Sakya and Kapil Karki 17.1 Background 250 17.2 Pharmacology 251 17.3 Structure?Activity Relationship (SAR) 253 17.4 Pharmacokinetics and Drug Metabolism 256 17.5 Efficacy and Safety 258 17.6 Synthesis of Donepezil 259 17.7 Synthesis of Rivastigmine 262 17.8 Synthesis of Galantamine 265 17.9 References 271 Chapter 18. Aprepitant (Emend), A NK1 Receptor Antagonist for the Treatment of Post-chemotherapy Emesis 275 John A. Lowe, III 18.1 Background 275 18.2 In Vitro Pharmacology and Structure-Activity Relationships 279 18.3 In Vivo Pharmacology 281 18.4 Pharmacokinetics and Drug Metabolism 282 18.5 Efficacy and Safety 282 18.6 Syntheses 283 18.7 References 289 Chapter 19. Armodafinil (Nuvigil), A Psychostimulant for the Treatment of Narcolepsy 291 Ji Zhang and Jason Crawford 19.1 Background 291 19.2 Pharmacology 293 19.3 Pharmacokinetics and Drug Metabolism 294 19.4 Efficacy and Safety 295 19.5 Synthesis 296 19.6 References 303 V. Miscellaneous 307 Chapter 20. Raloxifene (Evista), A Selective Estrogen Receptor Modulator (SERM) 309 Marta Piñeiro-Núñez 20.1 Background 309 20.2 Mechanism of Action 313 20.3 Pharmacokinetics and Drug Metabolism 313 20.4 Efficacy and Safety 314 20.5 Syntheses 315 20.6 References 325 Chapter 21. Latanoprost (Xalatan), A Prostanoid FP Agonist for Glaucoma 329 Sajiv K. Nair and Kevin E. Henegar 21.1 Background 329 21.2 Syntheses 331 21.3 References 337 Index 339


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Product Details
  • ISBN-13: 9780470525838
  • Publisher: John Wiley & Sons Inc
  • Publisher Imprint: John Wiley & Sons Inc
  • Depth: 25
  • Language: English
  • Returnable: N
  • Spine Width: 28 mm
  • Width: 183 mm
  • ISBN-10: 0470525835
  • Publisher Date: 27 Aug 2010
  • Binding: Hardback
  • Height: 257 mm
  • No of Pages: 376
  • Series Title: Wiley Series on Drug Synthesis
  • Weight: 793 gr


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