Current Drug Synthesis

Description

Current Drug Synthesis The latest entry in the widely read Drug Synthesis series In Current Drug Synthesis, accomplished medicinal chemist and researcher Dr. Jie Jack Li and 27 expert coauthors deliver an authoritative and comprehensive discussion of the medicinal chemistry of current drugs, as well as the cutting-edge science involved in their synthesis. The book demystifies the process of modern drug discovery for both industry practitioners and students, while capturing the state-of-the-art techniques used to discover some of the most impactful medicines on the market today. Covering six different disease areas – including infectious disease, cancer, cardiovascular and metabolic disease, the central nervous system, anti-inflammatory disease, and a miscellaneous section – the book explores 18 different drugs before concluding with chapters on computational drug discovery and peptide drugs. Each chapter includes coverage of background material on a relevant drug class or disease indication and key aspects of drug discovery, including structure-activity relationships, pharmacokinetics, drug metabolism, efficacy, and safety. Readers will also find: Thorough introductions to drugs for infectious diseases, including relebactam, vaborbactam, and baloxavir marboxilIn-depth treatments of cancer-treating drugs, including darolutamide, venetoclax, and osimertinib Comprehensive explorations of central nervous system drugs, including zuranolone and risdiplam Extensive discussions of computational drug discovery and peptide drugs Perfect for medicinal, organic, synthetic, and process chemists, Current Drug Synthesis will also earn a place in the libraries of research scientists working in lead optimization and process development, as well as graduate students studying organic chemistry, heterocyclic chemistry, or medicinal chemistry. Cover Title Page Copyright Contents Preface Contributing Authors PART I. INFECTIOUS DISEASE DRUGS Chapter 1. Relebactam (Recarbrio), A β-Lactamase Inhibitor for the Treatment of cIAI/cUTI/HABP/VABP 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 Summary 8 References Chapter 2. Vaborbactam (in Combination with Meropenem as Vabomere), a Non-β-Lactam β-Lactamase Inhibitor for Treatment of Complicated Urinary Tract Infections and Pyelonephritis 1 Background 2 Discovery Medicinal Chemistry 3 Vaborbactam/Vabomere Clinical Trials 4 Vaborbactam Medicinal Chemistry Synthesis 5 Vaborbactam Process Chemistry Synthesis 6 Conclusions 7 References Chapter 3. Baloxavir Marboxil (Xofluza), A Cap-Dependent Endonuclease Inhibitor for Treating Influenza 1 Background 2 Mechanism of Action 3 Structure–Activity Relationship 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 Summary 8 References Chapter 4. Process Chemistry Development of the HIV Protease Inhibitor Drug Kaletra: A Mixture of Ritonavir and Lopinavir 1 Background 2 Ritonavir Portion of Kaletra Synthesis 3 Discovery Synthesis of the Ritonavir Core 4 Discovery Synthesis of Ritonavir Wing Pieces 5 Large-Scale Process Chemistry Synthesis of the Ritonavir Core 6 Large-Scale Syntheses of the 5-Hydroxymethyl Thiazole Wing Portion 7 The Large-Scale Coupling of the Thiazole Wing Pieces and to the Core 8 Lopinavir Portion of Kaletra—Discovery Synthesis and Process Development 9 Discovery Synthesis of Lopinavir 10 Discovery Synthesis of Wing Pieces 11 Process Improvements to the Wing Pieces 12 Optimization of Lopinavir Synthesis with Intermediates 13 Conclusions 14 References Chapter 5. Eravacycline (Xerava), A Novel and Completely Synthetic Fluorocycline Antibiotic 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 Summary 8 References Chapter 6. Albuvirtide (Aikening), A gp41 Analog as an HIV-1 Fusion Inhibitor 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 Summary 8 References PART II. CANCER DRUGS Chapter 7. Darolutamide (Nubeqa): An Androgen Receptor Antagonist for Treating Nonmetastatic, Castration-Resis tant Prostate Cancer 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 The Future 8 References Chapter 8. Venetoclax (Venclexta): A BCL-2 Antagonist for Treating Chronic Lymphocytic Leukemia 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 Summary 8 References Chapter 9. Osimertinib (Tagrisso), A Potent and Selective Third-Generation EGFR Inhibitor for the Treatment of Both Sensitizing and T790M-Resistance Mutations 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 Summary 8 References Chapter 10. Sotorasib (LUMAKRA), An Irreversible Covalent Inhibitor of KRASG12C 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 Summary 8 References Chapter 11. Lorlatinib (Lorbrena), An ALK Inhibitor for Treating NSCLC 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 Summary 8 References Chapter 12. Niraparib (Zejula), A Small Molecule, PARP1/2 Inhibitor for Treating Breast, Ovarian, and Pancreatic Cancers 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 Summary 8 References Chapter 13. Selinexor (Xpovio), An XPO1 Inhibitor and a New Class of Therapeutics for Treating Multiple Myeloma 1 Exportin1 (XPO1) 2 Overview of Multiple Myeloma 3 Development of Selinexor 4 Pharmacology and Mechanism 5 Pharmacokinetics, Pharmacodynamics and Drug Metabolism 6 Efficacy and Safety 7 Syntheses 8 Summary and Future 9 References PART III. CNS DRUGS Chapter 14. Sage 217 (Zuranolone) for Treating Major of Depressive 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 Summary 8 References Chapter 15. Risdiplam (Evrysdi), A Small Molecule, SMN2-directed RNA Splicing Modifier for Treating Spinal Muscular Atrophy 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 Summary 8 References PART IV. MISCELLANEOUS DRUGS Chapter 16. Esaxerenone (Minnebro), An Oral, Nonsteroidal,Selective Mineralocorticoid Receptor Blocker for the Treatment of Essential Hypertension 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 Summary 8 References Chapter 17. Voclosporin (Lupkynis), A Macrocyclic Peptide Inhibitor of Calcineurin for the Treatment of Lupus Nephritis 1 Background 2 Pharmacology 3 Structure–Activity Relationship (SAR) 4 Pharmacokinetics and Drug Metabolism 5 Efficacy and Safety 6 Syntheses 7 References Chapter 18. Computational-Aided Drug Design 1 Background 2 Structure-based Drug Design (SBDD) 3 Ligand-based Drug Design (LBDD) 4 Summary 5 References Index EULA