Contemporary Drug Synthesis Preface v Trade Names and Their Corresponding USANs xi Acronyms and Abbreviations xiii Chapter 1. Antithrombotics: Ticlopidine (Ticlid) and Clopidogrel (Plavix) 1 Chapter 2. Anti-inflammatory Cyclooxygenase-2 Selective Inhibitors: Celecoxib (Celebrex) and Rofecoxib (Vioxx) 11 Chapter 3. H+/K+ -ATPase Inhibitors: Esomeprazole (Nexium) 21 Chapter 4. Protein-tyrosine Kinase Inhibitors: Imatnib (Gleevec) and Gefitinib (Iressa) 29 Chapter 5. Non-sedating Antihistamines 39 Chapter 6. Cosmeceuticals: Istretinoin (Accutane), Tazarotene (Tazorac), Minoxidil (Rogaine), and Finasteride (Propecia) 55 Chapter 7. Antibacterials: Ciprofloxacin (Cipro) and Linezolid (Zyvox) 75 Chapter 8.
Atypical Antupsychotics 89 Chapter 9. Atovastatin Calcium (Lipitor) 113 Chapter 10. Antidepressants 125 Chapter 11. Anti-obesity: Orlistat (Xenical) 149 Chapter 12. Triptans for Migrane 161 Chapter 13. PDE 5 Inhibitors for Erectile Dysfunction: Sildenafil (Viagra), Vardenafil (Levitra), and Tadalafil (Cialis) 189 Chapter 14. Antiasthmatics 201 Index 214 The Art of Drug Synthesis 1 THE ROLE OF MEDICINAL CHEMISTRY IN DRUG DISCOVERY 1 John A. Lowe, III 2 PROCESS RESEARCH: HOW MUCH? HOW SOON? 11 Neal G.
Anderson 3 AROMATASE INHIBITORS FOR BREAST CANCER: EXEMESTANE (AROMASIN), ANASTROZOLE (ARIMIDEX), AND LETROZOLE (FEMARA) 31 Jie Jack Li 4 QUINOLONE ANTIBIOTICS: LEVOFLOXACIN (LEVAQUIN), MOXIFLOXACIN (AVELOX), GEMIFLOXACIN (FACTIVE), AND GARENOXACIN (T-3811) 39 Chris Limberakis 5 TRIAZOLE ANTIFUNGALS: ITRACONAZOLE (SPORANOX), FLUCONAZOLE (DIFLUCAN), VORICONAZOLE (VFEND), AND FOSFLUCONAZOLE (PRODIF) 71 Andrew S. Bell 6 NON-NUCLEOSIDE HIV REVERSE TRANSCRIPTASE INHIBITORS 83 Arthur Harms 7 NEURAMINIDASE INHIBITORS FOR INFLUENZA: OSELTAMIVIR PHOSPHATE (TAMIFLU) AND ZANAMIVIR (RELENZA) 95 Douglas S. Johnson and Jie Jack Li 8 PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) AGONISTS FOR TYPE 2 DIABETES 117 Jin Li 9 ANGIOTENSIN AT1 ANTAGONISTS FOR HYPERTENSION 129 Larry Yet 10 LEADING ACE INHIBITORS FOR HYPERTENSION 143 Victor J. Cee and Edward J. Olhava 11 DIHYDROPYRIDINE CALCIUM CHANNEL BLOCKERS FOR HYPERTENSION 159 Daniel P. Christen 12 SECOND-GENERATION HMG-CoA REDUCTASE INHIBITORS 169 Jeffrey A. Pfefferkorn 13 CHOLESTEROL ABSORPTION INHIBITORS: EZETIMIBE (ZETIA) 183 Stuart B. Rosenblum 14 DUAL SELECTIVE SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS (SSNRIs) FOR DEPRESSION 199 Marta Pineiro-Nunez 15 GABAA RECEPTOR AGONISTS FOR INSOMNIA: ZOLPIDEM (AMBIEN), ZALEPLON (SONATA), ESZOPICLONE (ESTORRA, LUNESTA), AND INDIPLON 215 Peter R.
Guzzo 16 Alpha2Delta LIGANDS: NEURONTIN (GABAPENTIN) AND LYRICA (PREGABALIN) 225 Po-Wai Yuen 17 APPROVED TREATMENTS FOR ATTENTION DEFICIT HYPERACTIVITY DISORDER: AMPHETAMINE (ADDERALL), METHYLPHENIDATE (RITALIN), AND ATOMOXETINE (STRATERRA) 241 David L. Gray References 257 Index 261 Modern Drug Synthesis Preface xi Contributors xiii I. Infectious Diseases 1 Chapter 1. Raltegravir (Isentress), The First-in-class HIV-1 Integrase Inhibitor 3 Julianne A. Hunt Chapter 2. Maraviroc (Selzentry), The First-in-class CCR5 Antagonist for the Treatment of HIV 17 David Price Chapter 3. Darunavir (Prezista), A HIV-1 Protease Inhibitor for Treatment of Multidrug Resistant HIV 29 Arun K. Ghosh and Cuthbert D.
Martyr II. Cancer 45 Chapter 4. Decitabine (Dacogen), A DNA Methyltransferase Inhibitor for Cancer 47 Jennifer A. Van Camp Chapter 5. Capecitabine (Xeloda), An Oral Chemotherapy Agent 57 R. Jason Herr Chapter 6. Sorafenib (Nexavar), A Multi-kinase Inhibitor for Advanced Renal Cell Carcinoma and Unresectable Hepatocellular Carcinoma 73 Shuanghua Hu Chapter 7. Sunitinib (Sutent), An Angiogenesis Inhibitor 87 Martin Pettersson Chapter 8.
Bortezomib (Velcade), A First-in-class Proteasome Inhibitor 99 Benjamin S. Greener and David S. Millan Chapter 9. Pazopanib (Votrient), A VEGFR Tyrosine Kinase Inhibitor for Cancer 111 Ji Zhang and Jie Jack Li 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 Chapter 11.
Aliskiren (Tekturna), The First-in-class Renin Inhibitor for Hypertension 141 Victor J. Cee Chapter 12. Vernakalant (Kynapid), An Investigational Drug for the Treatment of Atrial Fibrillation 159 David L. Gray Chapter 13. Conivaptan (Vaprisol), Vasopressin V1a and V2 Antagonist for Hyponatremia 175 Brian A. Lanman Chapter 14. Rivaroxaban (Xarelto), A Factor Xa Inhibitor for the Treatment of Thrombotic Events 191 Ji Zhang and Jason Crawford Chapter 15. Endothelin Antagonists for the Treatment of Pulmonary Arterial Hypertension 207 David Edmonds 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 Chapter 17. Donepezil, Rivastigmine, Galantamine: Cholinesterase Inhibitors for Alzheimer''s Disease 249 Subas Sakya and Kapil Karki Chapter 18. Aprepitant (Emend), A NK1 Receptor Antagonist for the Treatment of Post-chemotherapy Emesis 275 John A. Lowe, III Chapter 19.
Armodafinil (Nuvigil), A Psychostimulant for the Treatment of Narcolepsy 291 Ji Zhang and Jason Crawford V. Miscellaneous 307 Chapter 20. Raloxifene (Evista), A Selective Estrogen Receptor Modulator (SERM) 309 Marta Piñeiro-Núñez Chapter 21. Latanoprost (Xalatan), A Prostanoid FP Agonist for Glaucoma 329 Sajiv K. Nair and Kevin E. Henegar Index 339 Innovative Drug Synthesis Preface xi Contributors xiii PART I. INFECTIOUS DISEASES 1 Chapter 1. Entecavir (Baraclude): A Carbocyclic Nucleoside for the Treatment of Chronic Hepatitis B 3 Chapter 2.
Telaprevir (Incivek) and Boceprevir (Victrelis): NS3/4A Inhibitors for Treatment for Hepatitis C Virus (HCV) 15 Chapter 3. Daclatasvir (Daklinza): The First-in-Class HCV NS5A Replication Complex Inhibitor 43 Chapter 4. Sofosbuvir (Sovaldi): The First-in-Class HCV NS5B Nucleotide Polymerase Inhibitor 61 Chapter 5. Bedaquiline (Sirturo): A Diarylquinoline that Blocks Tuberculosis ATP Synthase for the Treatment of Multi-Drug Resistant Tuberculosis 81 PART II. CANCER 99 Chapter 6. Enzalutamide (Xtandi): An Androgen Receptor Antagonist for Late-Stage Prostate Cancer 101 Chapter 7. Crizotinib (Xalkori): The First-in-Class ALK/ROS Inhibitor for Non-small Cell Lung Cancer 119 Chapter 8. Ibrutinib (Imbruvica): The First-in-Class Btk Inhibitor for Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom''s Macroglobulinemia 157 Chapter 9.
Palbociclib (Ibrance): The First-in-Class CDK4/6 Inhibitor for Breast Cancer 167 PART III. CARDIOVASCULAR DISEASES 197 Chapter 10. Ticagrelor (Brilinta) and Dabigatran Etexilate (Pradaxa): P2Y12 Platelet Inhibitors as Anti-coagulants 199 PART IV. CNS DRUGS 223 Chapter 11. Suvorexant (BELSOMRA): The First-in-Class Orexin Antagonist for Insomnia 225 Chapter 12. Lorcaserin (Belviq): Serotonin 2C Receptor Agonist for the Treatment of Obesity 243 Chapter 13. Fingolimod (Gilenya): The First Oral Treatment for Multiple Sclerosis 255 Chapter 14. Perampanel (Fycompa): AMPA Receptor Antagonist for the Treatment of Seizure 271 PART V.
ANTI-INFLAMMATORY DRUGS 283 Chapter 15. Tofacitinib (Xeljanz): The First-in-Class JAK Inhibitor for the Treatment of Rheumatoid Arthritis 285 PART VI. MISCELLANEOUS DRUGS 303 Chapter 16. Ivacaftor (Kalydeco): A CFTR Potentiator for the Treatment of Cystic Fibrosis 305 Chapter 17. Febuxostat (Uloric): A Xanthine Oxidase Inhibitor for the Treatment of Gout 317 Index 331.