{"product_id":"innovative-drug-synthesis-isbn-9781118820056","title":"Innovative Drug Synthesis","description":"This book covers all aspects of the medicinal chemistry of the latest drugs, and the cutting-edge science associated with them. Following the editors’ 3 successful drug synthesis books, this provides expert analysis of the pros and cons of different synthetic routes and demystifies the process of modern drug discovery for practitioners and researchers.\u003cbr\u003e\u003cbr\u003e \u003cul\u003e \u003cli\u003eSummarizes for each drug: respective disease area, important properties and SAR (structure-activity relationship), and chemical synthesis routes \/ options\u003c\/li\u003e \u003cli\u003eIncludes case studies in each chapter\u003c\/li\u003e \u003cli\u003eIllustrates how chemistry, biology, pharmacokinetics, and a host of disciplines come together to produce successful medicines\u003c\/li\u003e \u003cli\u003eExplains the advantages of process synthesis versus the synthetic route for drug discovery\u003c\/li\u003e \u003c\/ul\u003e \u003cp\u003ePreface xi\u003c\/p\u003e \u003cp\u003eContributors xiii\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART I. INFECTIOUS DISEASES 1\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 1. Entecavir (Baraclude): A Carbocyclic Nucleoside for the Treatment of Chronic Hepatitis B 3\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 3\u003c\/p\u003e \u003cp\u003e2 Pharmacology 5\u003c\/p\u003e \u003cp\u003e3 Structure–Activity Relationship (SAR) 6\u003c\/p\u003e \u003cp\u003e4 Pharmacokinetics and Drug Metabolism 7\u003c\/p\u003e \u003cp\u003e5 Efficacy and Safety 8\u003c\/p\u003e \u003cp\u003e6 Syntheses 8\u003c\/p\u003e \u003cp\u003e7 References 14\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 2. Telaprevir (Incivek) and Boceprevir (Victrelis): NS3\/4A Inhibitors for Treatment for Hepatitis C Virus (HCV) 15\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 16\u003c\/p\u003e \u003cp\u003e2 Pharmacology 16\u003c\/p\u003e \u003cp\u003e3 Structure–Activity Relationship (SAR) 17\u003c\/p\u003e \u003cp\u003e4 PK and Drug Metabolism 20\u003c\/p\u003e \u003cp\u003e5 Efficacy and Safety 22\u003c\/p\u003e \u003cp\u003e6 Synthesis 24\u003c\/p\u003e \u003cp\u003e7 Conclusions 38\u003c\/p\u003e \u003cp\u003e8 References 39\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 3. Daclatasvir (Daklinza): The First-in-Class HCV NS5A Replication Complex Inhibitor 43\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 43\u003c\/p\u003e \u003cp\u003e2 Discovery Medicinal Chemistry 45\u003c\/p\u003e \u003cp\u003e3 Mode of Action 48\u003c\/p\u003e \u003cp\u003e4 Pharmacokinetics and Drug Metabolism 49\u003c\/p\u003e \u003cp\u003e5 Efficacy and Safety 49\u003c\/p\u003e \u003cp\u003e6 Syntheses 52\u003c\/p\u003e \u003cp\u003e7 References 57\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 4. Sofosbuvir (Sovaldi): The First-in-Class HCV NS5B Nucleotide Polymerase Inhibitor 61\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 61\u003c\/p\u003e \u003cp\u003e2 Pharmacology 63\u003c\/p\u003e \u003cp\u003e3 Structure–Activity Relationship (SAR) 64\u003c\/p\u003e \u003cp\u003e4 Pharmacokinetics and Drug Metabolism 68\u003c\/p\u003e \u003cp\u003e5 Efficacy and Safety 69\u003c\/p\u003e \u003cp\u003e6 Syntheses 72\u003c\/p\u003e \u003cp\u003e7 Summary 76\u003c\/p\u003e \u003cp\u003e8 References 76\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 5. Bedaquiline (Sirturo): A Diarylquinoline that Blocks Tuberculosis ATP Synthase for the Treatment of Multi-Drug Resistant Tuberculosis 81\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 81\u003c\/p\u003e \u003cp\u003e2 Pharmacology 84\u003c\/p\u003e \u003cp\u003e3 Structure–Activity Relationship (SAR) 85\u003c\/p\u003e \u003cp\u003e4 Pharmacokinetics and Drug Metabolism 86\u003c\/p\u003e \u003cp\u003e5 Efficacy and Safety 87\u003c\/p\u003e \u003cp\u003e6 Syntheses 88\u003c\/p\u003e \u003cp\u003e7 References 96\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART II. CANCER 99\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 6. Enzalutamide (Xtandi): An Androgen Receptor Antagonist for Late-Stage Prostate Cancer 101\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 101\u003c\/p\u003e \u003cp\u003e2 Pharmacology 103\u003c\/p\u003e \u003cp\u003e3 Structure–Activity Relationship (SAR) 104\u003c\/p\u003e \u003cp\u003e4 Pharmacokinetics and Drug Metabolism 108\u003c\/p\u003e \u003cp\u003e5 Efficacy and Safety 109\u003c\/p\u003e \u003cp\u003e6 Synthesis 111\u003c\/p\u003e \u003cp\u003e7 Compounds in Development 114\u003c\/p\u003e \u003cp\u003e8 References 115\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 7. Crizotinib (Xalkori): The First-in-Class ALK\/ROS Inhibitor for Non-small Cell Lung Cancer 119\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background: Non-small Cell Lung Cancer (NSCLC) Treatment 119\u003c\/p\u003e \u003cp\u003e2 Discovery Medicinal Chemistry Effort: SAR and Lead Optimization of Compound 2 as a c-Met Inhibitor 120\u003c\/p\u003e \u003cp\u003e3 ALK and ROS in Non-small Cell Lung Cancer (NSCLC) Treatment 127\u003c\/p\u003e \u003cp\u003e4 Preclinical Model Tumor Growth Inhibition Efficacy and Pharmacology 127\u003c\/p\u003e \u003cp\u003e5 Human Clinical Trials 128\u003c\/p\u003e \u003cp\u003e6 Introduction to the Synthesis and Limitations of the Discovery Route to Crizotinib Analogs 129\u003c\/p\u003e \u003cp\u003e7 Process Chemistry: Initial Improvements 131\u003c\/p\u003e \u003cp\u003e8 Process Chemistry: Enabling Route to Crizotinib 135\u003c\/p\u003e \u003cp\u003e9 Development of the Commercial Process 141\u003c\/p\u003e \u003cp\u003e10 Commercial Synthesis of Crizotinib 147\u003c\/p\u003e \u003cp\u003e11 References 152\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 8. Ibrutinib (Imbruvica): The First-in-Class Btk Inhibitor for Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia 157\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 157\u003c\/p\u003e \u003cp\u003e2 Pharmacology 159\u003c\/p\u003e \u003cp\u003e3 Structure–Activity Relationship (SAR) 159\u003c\/p\u003e \u003cp\u003e4 Pharmacokinetics and Drug Metabolism 161\u003c\/p\u003e \u003cp\u003e5 Efficacy and Safety 161\u003c\/p\u003e \u003cp\u003e6 Syntheses 162\u003c\/p\u003e \u003cp\u003e7 References 164\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 9. Palbociclib (Ibrance): The First-in-Class CDK4\/6 Inhibitor for Breast Cancer 167\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 167\u003c\/p\u003e \u003cp\u003e2 Pharmacology 168\u003c\/p\u003e \u003cp\u003e3 Discovery Program 169\u003c\/p\u003e \u003cp\u003e4 Preclinical Profile of Palbociclib 175\u003c\/p\u003e \u003cp\u003e5 Clinical Profile of Palbociclib 176\u003c\/p\u003e \u003cp\u003e6 Early Process Development for Palbociclib 177\u003c\/p\u003e \u003cp\u003e7 Commercial Process for Preparation of Palbociclib 192\u003c\/p\u003e \u003cp\u003e8 References 193\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART III. CARDIOVASCULAR DISEASES 197\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 10. Ticagrelor (Brilinta) and Dabigatran Etexilate (Pradaxa): P2Y12 Platelet Inhibitors as Anti-coagulants 199\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Introduction 200\u003c\/p\u003e \u003cp\u003e2 Dabigatran Etexilate 200\u003c\/p\u003e \u003cp\u003e3 Ticagrelor 207\u003c\/p\u003e \u003cp\u003e4 The Future 219\u003c\/p\u003e \u003cp\u003e5 References 220\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART IV. CNS DRUGS 223\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 11. Suvorexant (BELSOMRA): The First-in-Class Orexin Antagonist for Insomnia 225\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 225\u003c\/p\u003e \u003cp\u003e2 Pharmacology 229\u003c\/p\u003e \u003cp\u003e3 Pharmacokinetics and Drug Metabolism 230\u003c\/p\u003e \u003cp\u003e4 Efficacy and Safety 231\u003c\/p\u003e \u003cp\u003e5 Structure–Activity Relationship (SAR) 231\u003c\/p\u003e \u003cp\u003e6 Synthesis 233\u003c\/p\u003e \u003cp\u003e7 References 239\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 12. Lorcaserin (Belviq): Serotonin 2C Receptor Agonist for the Treatment of Obesity 243\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 243\u003c\/p\u003e \u003cp\u003e2 Pharmacology 245\u003c\/p\u003e \u003cp\u003e3 Structure–Activity Relationship (SAR) 246\u003c\/p\u003e \u003cp\u003e4 Pharmacokinetics and Drug Metabolism 248\u003c\/p\u003e \u003cp\u003e5 Efficacy and Safety 249\u003c\/p\u003e \u003cp\u003e6 Synthesis 250\u003c\/p\u003e \u003cp\u003e7 References 253\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 13. Fingolimod (Gilenya): The First Oral Treatment for Multiple Sclerosis 255\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 255\u003c\/p\u003e \u003cp\u003e2 Structure–Activity Relationship (SAR) 257\u003c\/p\u003e \u003cp\u003e3 Pharmacology 259\u003c\/p\u003e \u003cp\u003e4 Human Pharmacokinetics and Drug Metabolism 260\u003c\/p\u003e \u003cp\u003e5 Efficacy and Safety 261\u003c\/p\u003e \u003cp\u003e6 Syntheses 263\u003c\/p\u003e \u003cp\u003e7 Summary 268\u003c\/p\u003e \u003cp\u003e8 References 269\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 14. Perampanel (Fycompa): AMPA Receptor Antagonist for the Treatment of Seizure 271\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 271\u003c\/p\u003e \u003cp\u003e2 Pharmacology 273\u003c\/p\u003e \u003cp\u003e3 Structure–Activity Relationship (SAR) 274\u003c\/p\u003e \u003cp\u003e4 Pharmacokinetics and Drug Metabolism 276\u003c\/p\u003e \u003cp\u003e5 Efficacy and Safety 277\u003c\/p\u003e \u003cp\u003e6 Syntheses 278\u003c\/p\u003e \u003cp\u003e7 References 280\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART V. ANTI-INFLAMMATORY DRUGS 283\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 15. Tofacitinib (Xeljanz): The First-in-Class JAK Inhibitor for the Treatment of Rheumatoid Arthritis 285\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 285\u003c\/p\u003e \u003cp\u003e2 Structure–Activity Relationships (SAR) 287\u003c\/p\u003e \u003cp\u003e3 Safety, Pharmacology and Pharmacokinetics 289\u003c\/p\u003e \u003cp\u003e4 Syntheses 290\u003c\/p\u003e \u003cp\u003e5 Development of the Commercial Manufacturing Process 292\u003c\/p\u003e \u003cp\u003e6 References 300\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART VI. MISCELLANEOUS DRUGS 303\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 16. Ivacaftor (Kalydeco): A CFTR Potentiator for the Treatment of Cystic Fibrosis 305\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 305\u003c\/p\u003e \u003cp\u003e2 Pharmacology 306\u003c\/p\u003e \u003cp\u003e3 Structure–Activity Relationship (SAR) 307\u003c\/p\u003e \u003cp\u003e4 Pharmacokinetics and Drug Metabolism 308\u003c\/p\u003e \u003cp\u003e5 Efficacy and Safety 310\u003c\/p\u003e \u003cp\u003e6 Syntheses 311\u003c\/p\u003e \u003cp\u003e7 References 315\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 17. Febuxostat (Uloric): A Xanthine Oxidase Inhibitor for the Treatment of Gout 317\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Background 317\u003c\/p\u003e \u003cp\u003e2 Pharmacology 319\u003c\/p\u003e \u003cp\u003e3 Structure–Activity Relationship (SAR) 320\u003c\/p\u003e \u003cp\u003e4 Pharmacokinetics and Drug Metabolism 321\u003c\/p\u003e \u003cp\u003e5 Efficacy and Safety 322\u003c\/p\u003e \u003cp\u003e6 Syntheses 323\u003c\/p\u003e \u003cp\u003e7 Drug in Development: Lesinurad Sodium 328\u003c\/p\u003e \u003cp\u003e8 References 330\u003c\/p\u003e \u003cp\u003eIndex 331\u003c\/p\u003e  \u003cp\u003e\u003cb\u003eJie Jack Li\u003c\/b\u003e is an Associate Professor of chemistry at the University of San Francisco. Previously, he was a Discovery Chemist at Bristol-Myers Squibb and Pfizer. He has authored or edited over 20 books and several of those were published by Wiley, including \u003ci\u003eDrug Discovery: Practices, Processes, and Perspectives, Heterocyclic Chemistry in Drug Discovery, Name Reactions in Heterocyclic Chemistry, Name Reactions for Functional Group Transformations, Contemporary Drug Synthesis, The Art of Drug Synthesis, and Modern Drug Synthesis\u003c\/i\u003e \u003c\/p\u003e\u003cp\u003e\u003cb\u003eDouglas S. Johnson\u003c\/b\u003e is a Research Fellow and Head of Chemical Biology in the Neuroscience Medicinal Chemistry group at Pfizer Worldwide Research and Development. He is a co-author on more than 75 publications and patents and is a co-author of the book \u003ci\u003eContemporary Drug Synthesis and is an editor of The Art of Drug Synthesis, and Modern Drug Synthesis\u003c\/i\u003e (all published by Wiley).    \u003c\/p\u003e\u003cp\u003e\u003cb\u003eDiscover the cutting-edge science driving the medicinal chemistry and synthesis of the latest drugs\u003c\/b\u003e \u003c\/p\u003e\u003cp\u003eContinuing the tradition of the acclaimed prior volumes on drug synthesis, \u003ci\u003eInnovative Drug Synthesis\u003c\/i\u003e illustrates how chemistry, biology, pharmacokinetics, and related disciplines come together to produce successful medicines. This book covers all aspects of the medicinal chemistry of the latest drugs and the cutting-edge science associated with them. With authoritative coverage by distinguished editors and authors analyzing the pros and cons of different synthetic routes, the book demystifies the process of modern drug discovery for practitioners and researchers. \u003c\/p\u003e\u003cp\u003eOther highlights include: \u003c\/p\u003e\u003cul\u003e \u003cli\u003eSummary of respective disease area, important properties and SAR (structure–activity relationship), and chemical synthesis routes\/options for each covered drug\u003c\/li\u003e \u003cli\u003eA step-by-step breakdown of today's drug discovery process for professionals and students\u003c\/li\u003e \u003cli\u003eChapters on drugs that have achieved breakthrough therapy designation such as sofosbuvir, palbociclib, and more\u003c\/li\u003e \u003c\/ul\u003e \u003cp\u003e\u003ci\u003eInnovative Drug Synthesis\u003c\/i\u003e shows that whether drug synthesis is in early development or the process stage, the ability to design elegant and economical synthetic routes is often a major factor making a drug a commercial winner. Easy to follow and stacked with valuable information on the present and future direction of medicinal chemistry, \u003ci\u003eInnovative Drug Synthesis\u003c\/i\u003e paints a clear and complete picture of this complex subject.\u003c\/p\u003e","brand":"Wiley","offers":[{"title":"Default Title","offer_id":47989427077349,"sku":"NP9781118820056","price":139.95,"currency_code":"USD","in_stock":false}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/1842\/7735\/files\/9781118820056.jpg?v=1761784062","url":"https:\/\/k12savings.com\/products\/innovative-drug-synthesis-isbn-9781118820056","provider":"K12savings","version":"1.0","type":"link"}