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. Summarizes for each drug: respective disease area, important properties and SAR (structure–activity relationship), and chemical synthesis routes / options Includes case studies in each chapter Illustrates how chemistry, biology, pharmacokinetics, and a host of disciplines come together to produce successful medicines Explains the advantages of process synthesis versus the synthetic route for drug discovery INDICE: PART I. INFECTIOUS DISEASES .1. Entecavir (Baraclude): A Carbocyclic Nucleoside for the Treatment of Chronic Hepatitis BJie Jack Li .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 .2. Telaprevir (Incivek) and Boceprevir (Victrelis): NS3/4A Inhibitors for Treatment forHepatitis C Virus (HCV)Amy B. Dounay .2.1 Background .2.2 Pharmacology .2.3 Structure Activity Relationship (SAR) .2.4 Pharmacokinetics and Drug Metabolism .2.5 Efficacy and Safety .2.6 Synthesis .2.7 Conclusions .3. Daclatasvir (Daklinza): The First–in–Class HCV NS5A Replication Complex InhibitorMakonen Belema, Shawn K. Pack and Nicholas A. Meanwell .3.1 Background .3.2 Discovery Medicinal Chemistry .3.3 Mode of Action .3.4 Pharmacokinetics and Drug Metabolism .3.5 Efficacy and Safety .3.6 Syntheses .4. Sofosbuvir (Sovaldi): The First–in–Class HCV NS5B Nucleotide Polymerase InhibitorRaymond F. Schinazi, Junxing Shi and Tony Whitaker .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 Summary .5. Bedaquiline (Sirturo): Diarylquinoline that Blocks Tuberculosis ATP Synthase for the Treatment of Multi–Drug Resistant TuberculosisElizabeth N. Cruz, Amanda N. Moules and Jie Jack Li .5.1 Background .5.2 Pharmacology .5.3 Structure Activity Relationship (SAR) .5.4 Pharmacokinetics and Drug Metabolism .5.5 Efficacy and Safety .5.6 Syntheses .PART II. CANCER .6. Enzalutamide: An Androgen Receptor Antagonist for Late–Stage Prostate CancerSha Lou and Ji Zhang .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 Synthesis .6.7 Compounds in Development .7. Crizotinib (Xalkori): The First–in–Class ALK/ROS Inhibitor for Non–small Cell Lung CancerPei–Pei Kung, Ricky Anthony Jones and Paul Richardson .7.1 Background .7.2 Discovery Medicinal Chemistry Effort .7.3 ALK and ROS in Non–small Cell Lung Cancer (NSCLC) Treatment .7.4 Pre–clinical Model Tumor Growth Inhibition Efficacy and Pharmacology .7.5 Human Clinical Trials .7.6 Introduction to the Synthesis and Limitations of the Discovery Route to Crizotinib Analogs .7.7 Process Chemistry Initial Improvements .7.8 Process Chemistry Enabling Route to Crizotinib .7.9 Development of the Commercial Process .7.10 Commercial Synthesis of Crizotinib .8. Ibrutinib (Imbruvica): The First–in–Class Btk Inhibitor for Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia and Waldenstrom?s MacroglobulinemiaHui Liu and Zhengying Pan .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 Synthesis .9. Palbociclib (Ibrance): The First–in–Class CDK4/6 Inhibitor for Breast CancerPeter L. Toogood and Nathan D. Ide .9.1 Background .9.2 Pharmacology .9.3 Discovery Program .9.4 Preclinical Profile of Palbociclib .9.5 Clinical Profile of Palbociclib .9.6 Early Process Development for Palbociclib .9.7 Commercial Process for Preparation of Palbociclib .PART III. CARDIOVASCULAR DISEASES .10. Ticagrelor (Brilinta) and Dabigatran Etexilate (Pradaxa): P2Y12 Platelet Inhibitors as Anti–coagulantsWenhao Hu and Shunying Liu .10.1 Background .10.2 Dabigatran Etexilate .10.3 Ticagrelor .10.4 The Future .PART IV. CNS DRUGS .11. Suvorexant (BELSOMRA): OrexinReceptor Antagonist for the Treatment of InsomniaNadia M. Ahmad .11.1 Background .11.2 Pharmacology .11.3 Pharmacokinetics and Drug Metabolism .11.4 Efficacy and Safety .11.5 Structure Activity Relationship (SAR) .11.6 Synthesis .12. Lorcaserin (Belviq): Serotonin 2C Receptor Agonist for the Treatment of ObesityTaylor D. Krueger, Emily S. Murzinski, Karla E. Rodriguez and Jie Jack Li .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 Synthesis .13. Fingolimod (Gilenya): The First Oral Treatment for Multiple SclerosisChristopher W. am Ende and Jamison B. Tuttle .13.1 Background .13.2 Structure Activity Relationship (SAR) .13.3 Pharmacology .13.4 Human Pharmacokinetics and Drug Metabolism .13.5 Efficacy and Safety .13.6 Syntheses .13.7 Summary .14. Perampanel (Fycompa): AMPA Receptor Antagonist for the Treatment of SeizureNandini C. Patel .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 .PART V. ANTI–INFLAMMATORY DRUGS .15. Tofacitinib (Xeljanz): The First–in–Class JAK Inhibitor for the Treatment of Rheumatoid ArthritisRobert W. Dugger, Mark E. Flanagan and Rajappa Vaidyanathan .15.1 Background .15.2 Structure Activity Relationship (SAR) .15.3 Safety, Pharmacology and Pharmacokinetics .15.4 Syntheses .15.5 Development of the Commercial Manufacturing Process .PART VI. MISCELLANEOUS DRUGS .16. Ivacaftor (Kalydeco): A CFTR Potentiator for the Treatment of Cystic FibrosisCho K. Lai, Theresa V. Song, and Jie Jack Li .16.1 Background .16.2 Pharmacology .16.3 Structure Activity Relationship (SAR) .16.4 Pharmacokinetics and Drug Metabolism .16.5 Efficacy and Safety .16.6 Syntheses .17. Febuxostat (Uloric): Xanthine Oxidase Inhibitor for the Treatment of GoutJi Zhang and Yingjun Zhang .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 Syntheses .17.7 Drug in Development: Lesinurad Sodium .References .Index
- ISBN: 978-1-118-82005-6
- Editorial: Wiley–Blackwell
- Encuadernacion: Cartoné
- Páginas: 360
- Fecha Publicación: 09/12/2015
- Nº Volúmenes: 1
- Idioma: Inglés