Modern Drug Synthesis

JIE JACK LI is a chemist at Bristol-Myers Squibb Company in Wallingford, Connecticut. He is the coauthor of various books, including Palladium in Heterocyclic Chemistry, Name Reactions: A Collection of Detailed Reaction Mechanisms and Synthetic Applications, Name Reactions in Heterocyclic Chemistry, Contemporary Drug Synthesis, The Art of Drug Synthesis, Name Reactions for Functional Group Transformations, Name Reactions for Homologations, Parts 1 and 2, and Name Reactions for Carbocyclic Ring Formations. DOUGLAS JOHNSON is a medicinal chemist and project leader at Pfizer in Groton, Connecticut. He is a coauthor on more than forty publications and patents, including the books The Art of Drug Synthesis and Contemporary Drug Synthesis.

Preface. Contributors. I. Infectious Diseases. Chapter 1. Raltegravir (Isentress), The First-in-class HIV-1 Integrase Inhibitor ( Julianne A. Hunt ). 1.1 Background. 1.2 Pharmacology. 1.3 Structure-Activity Relationship (SAR). 1.4 Pharmacokinetics and Drug Metabolism. 1.5 Efficacy and Safety. 1.6 Syntheses. 1.7 References. Chapter 2. Maraviroc (Selzentry), The First-in-class CCR5 Antagonist for the Treatment of HIV ( David Price ). 2.1 Background. 2.2 Structure-Activity Relationship (SAR). 2.3 Pharmacokinetics and Safety. 2.4 Syntheses. 2.5 References. Chapter 3. Darunavir (Prezista), A HIV-1 Protease Inhibitor for Treatment of Multidrug Resistant HIV ( Arun K. Ghosh and Cuthbert D. Martyr ). 3.1 Background. 3.2 Pharmacology. 3.3 Structure-Activity Relationship (SAR). 3.4 Pharmacokinetics and Drug Metabolism. 3.5 Efficacy and Safety. 3.6 Syntheses. 3.7 References. II. Cancer. Chapter 4. Decitabine (Dacogen), A DNA Methyltransferase Inhibitor for Cancer ( Jennifer A. Van Camp ). 4.1 Background. 4.2 Pharmacology. 4.3 Structure-Activity Relationship (SAR). 4.4 Pharmacokinetics and Drug Metabolism. 4.5 Efficacy and Safety. 4.6 Syntheses. 4.7 References. Chapter 5. Capecitabine (Xeloda), An Oral Chemotherapy Agent ( R. Jason Herr ). 5.1 Background. 5.2 Pharmacology. 5.3 Structure-Activity Relationship (SAR). 5.4 Pharmacokinetics and Efficacy. 5.5 Syntheses. 5.6 References. Chapter 6. Sorafenib (Nexavar), A Multi-kinase Inhibitor for Advanced Renal Cell Carcinoma and Unresectable Hepatocellular Carcinoma ( Shuanghua Hu ). 6.1 Background. 6.2 Pharmacology. 6.3 Structure-Activity Relationship (SAR). 6.4 Pharmacokinetics and Drug Metabolism. 6.5 Efficacy and Safety. 6.6 Syntheses. 6.7 References. Chapter 7. Sunitinib (Sutent), An Angiogenesis Inhibitor ( Martin Pettersson ). 7.1 Background. 7.2 Discovery and Development. 7.3 Syntheses. 7.3.1 Discovery Route. 7.3.2 Process Route. 7.4 References. Chapter 8. Bortezomib (Velcade), A First-in-class Proteasome Inhibitor ( Benjamin S. Greener and David S. Millan ). 8.1 Background. 8.2 Pharmacology. 8.3 Structure-Activity Relationship (SAR). 8.4 Pharmacokinetics and Drug Metabolism. 8.5 Efficacy and Safety. 8.6 Syntheses. 8.7 References. Chapter 9. Pazopanib (Votrient), A VEGFR Tyrosine Kinase Inhibitor for Cancer ( Ji Zhang and Jie Jack Li ). 9.1 Background. 9.2 Pharmacology. 9.3 Structure?Activity Relationship (SAR). 9.4 Pharmacokinetics and Drug Metabolism. 9.5 Efficacy and Safety. 9.6 Syntheses. 9.7 Other VEGFR Inhibitors in Development: Vandetanib and Cediranib. 9.8 References. III. Cardiovascular and Metabolic Diseases. Chapter 10. Sitagliptin (Januvia), A Treatment for Type 2 Diabetes ( Scott D. Edmondson, Feng Xu, and Joseph D. Armstrong III ). 10.1 Background. 10.2 Pharmacology. 10.3 Structure-Activity Relationship (SAR). 10.4 Pharmacokinetics and Drug Metabolism. 10.5 Efficacy and Safety. 10.6 Syntheses. 10.7 References. Chapter 11. Aliskiren (Tekturna), The First-in-class Renin Inhibitor for Hypertension ( Victor J. Cee ). 11.1 Background. 11.2 Pharmacology. 11.3 Structure-Activity Relationship (SAR). 11.4 Pharmacokinetics and Drug Metabolism. 11.5 Efficacy and Safety. 11.6 Syntheses. 11.7 References. Chapter 12. Vernakalant (Kynapid), An Investigational Drug for the Treatment of Atrial Fibrillation ( David L. Gray ). 12.1 Background. 12.2 Pharmacology. 12.3 Structure-Activity Relationship (SAR). 12.4 Pharmacokinetics and Drug Metabolism. 12.5 Efficacy and Safety. 12.6 Syntheses. 12.7 References. Chapter 13. Conivaptan (Vaprisol), Vasopressin V1a and V2 Antagonist for Hyponatremia ( Brian A. Lanman ). 13.1 Background. 13.2 Pharmacology. 13.3 Structure-Activity Relationship (SAR). 13.4 Pharmacokinetics and Drug Metabolism. 13.5 Efficacy and Safety. 13.6 Syntheses. 13.7 References. Chapter 14. Rivaroxaban (Xarelto), A Factor Xa Inhibitor for the Treatment of Thrombotic Events ( Ji Zhang and Jason Crawford ). 14.1 Background. 14.2 Pharmacology. 14.3 Structure?Activity Relationship (SAR). 14.4 Pharmacokinetics and Drug Metabolism. 14.5 Efficacy and Safety. 14.6 Syntheses. 14.7 Compounds in Development: Apixaban and Otamixaban. 14.8 References. Chapter 15. Endothelin Antagonists for the Treatment of Pulmonary Arterial Hypertension ( David Edmonds ). 15.1 Background. 15.2 Treatment of PAH. 15.3 Endothelin Antagonists. 15.4 Synthesis of Bosentan. 15.5 Synthesis of Sitaxsentan. 15.6 Synthesis of Ambrisentan. 15.7 Conclusion. 15.8 References. IV. Central Nervous System Diseases. Chapter 16. Varenicline (Chantix), An alpha4beta2 Nicotinic Receptor Partial Agonist for Smoking Cessation ( Jotham W. Coe, Frank R. Busch and Robert A. Singer ). 16.1 Background. 16.2 Discovery Chemistry Program. 16.3 Pharmacology. 16.4 Pharmacokinetics and Drug Metabolism. 16.5 Efficacy and Safety. 16.6 Syntheses. 16.7 References. Chapter 17. Donepezil, Rivastigmine, Galantamine: Cholinesterase Inhibitors for Alzheimer's Disease ( Subas Sakya and Kapil Karki ). 17.1 Background. 17.2 Pharmacology. 17.3 Structure?Activity Relationship (SAR). 17.4 Pharmacokinetics and Drug Metabolism. 17.5 Efficacy and Safety. 17.6 Synthesis of Donepezil. 17.7 Synthesis of Rivastigmine. 17.8 Synthesis of Galantamine. 17.9 References. Chapter 18. Aprepitant (Emend), A NK1 Receptor Antagonist for the Treatment of Post-chemotherapy Emesis ( John A. Lowe, III ). 18.1 Background. 18.2 In Vitro Pharmacology and Structure-Activity Relationships. 18.3 In Vivo Pharmacology. 18.4 Pharmacokinetics and Drug Metabolism. 18.5 Efficacy and Safety. 18.6 Syntheses. 18.7 References. Chapter 19. Armodafinil (Nuvigil), A Psychostimulant for the Treatment of Narcolepsy ( Ji Zhang and Jason Crawford ). 19.1 Background. 19.2 Pharmacology. 19.3 Pharmacokinetics and Drug Metabolism. 19.4 Efficacy and Safety. 19.5 Synthesis. 19.6 References. V. Miscellaneous. Chapter 20. Raloxifene (Evista), A Selective Estrogen Receptor Modulator (SERM) ( Marta Pi?eiro-Nu?ez ). 20.1 Background. 20.2 Mechanism of Action. 20.3 Pharmacokinetics and Drug Metabolism. 20.4 Efficacy and Safety. 20.5 Syntheses. 20.6 References. Chapter 21. Latanoprost (Xalatan), A Prostanoid FP Agonist for Glaucoma ( Sajiv K. Nair and Kevin E. Henegar ). 21.1 Background. 21.2 Syntheses. 21.3 References. Index.