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      Current Drug Synthesis

      AvJie Jack Li

      Inbunden, Engelska, 2022

      Del i serien Wiley Series on Drug Synthesis

      2 049 kr

      Beställningsvara. Skickas inom 5-8 vardagar. Fri frakt över 249 kr.

      Beskrivning

      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 drugsPerfect 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.

      Produktinformation

      • Utgivningsdatum:2022-11-17
      • Mått:10 x 10 x 10 mm
      • Vikt:454 g
      • Format:Inbunden
      • Språk:Engelska
      • Serie:Wiley Series on Drug Synthesis
      • Antal sidor:400
      • Förlag:John Wiley & Sons Inc
      • ISBN:9781119847250

      Utforska kategorier

      • Farmakologi inom Medicin
      • Organisk kemi inom Naturvetenskap och teknik

      Mer om författaren

      Jie Jack Li, PhD, is the CSO of GenHouse Bio. Previously, he was VP of Discovery Chemistry at ChemPartner, an Associate Professor of Chemistry at the University of San Francisco and a Medicinal Chemist at Pfizer and Bristol-Myers Squibb. He has authored or edited over 30 books, including Medicinal Chemistry for Practitioners published by Wiley in 2020.

      Innehållsförteckning

      • Preface xi Contributing Authors xiiiPart I Infectious Disease Drugs 1 Chapter 1 Relebactam (Recarbrio), A β-Lactamase Inhibitor for the Treatment of cIAI/cUTI/HABP/ VABP 31 Background 32 Pharmacology 53 Structure–Activity Relationship (SAR) 64 Pharmacokinetics and Drug Metabolism 95 Efficacy and Safety 106 Syntheses 107 Summary 148 References 14Chapter 2 Vaborbactam (in Combination with Meropenem as Vabomere), a Non-β-Lactam β-Lactamase Inhibitor for Treatment of Complicated Urinary Tract Infections and Pyelonephritis 171 Background 172 Discovery Medicinal Chemistry 213 Vaborbactam/Vabomere Clinical Trials 274 Vaborbactam Medicinal Chemistry Synthesis 295 Vaborbactam Process Chemistry Synthesis 306 Conclusions 377 References 38Chapter 3 Baloxavir Marboxil (Xofluza), A Cap-Dependent Endonuclease Inhibitor for Treating Influenza 41 1 Background 412 Mechanism of Action 433 Structure–Activity Relationship 454 Pharmacokinetics and Drug Metabolism 495 Efficacy and Safety 506 Syntheses 507 Summary 548 References 54Chapter 4 Process Chemistry Development of the HIV Protease Inhibitor Drug Kaletra: A Mixture of Ritonavir and Lopinavir 57 1 Background 582 Ritonavir Portion of Kaletra Synthesis 583 Discovery Synthesis of the Ritonavir Core 604 Discovery Synthesis of Ritonavir Wing Pieces 63  5 Large-Scale Process Chemistry Synthesis of the  Ritonavir Core 656 Large-Scale Syntheses of the 5-Hydroxymethyl  Thiazole Wing Portion 697 The Large-Scale Coupling of the Thiazole  Wing Pieces to the Core 708 Lopinavir Portion of Kaletra—  Discovery Synthesis and Process Development 729 Discovery Synthesis of Lopinavir 7310 Discovery Synthesis of Wing Pieces 7411 Process Improvements to the Wing Pieces 7612 Optimization of Lopinavir Synthesis with Intermediates 7813 Conclusions 8114 References 81Chapter 5 Eravacycline (Xerava), A Novel and Completely Synthetic Fluorocycline Antibiotic 85 1 Background 852 Pharmacology 893 Structure–Activity Relationship (SAR) 914 Pharmacokinetics and Drug Metabolism 935 Efficacy and Safety 936 Syntheses 937 Summary 988 References 99Chapter 6 Albuvirtide (Aikening), A gp41 Analog as an HIV-1 Fusion Inhibitor 101 1 Background 1012 Pharmacology 1023 Structure–Activity Relationship (SAR) 1064 Pharmacokinetics and Drug Metabolism 1075 Efficacy and Safety 1106 Syntheses 1127 Summary 1148 References 115Part II Cancer Drugs 119 Chapter 7 Darolutamide (Nubeqa): An Androgen Receptor  Antagonist for Treating Nonmetastatic, Castration-Resistant 121 1 Background 1212 Pharmacology 1243 Structure–Activity Relationship (SAR) 1264 Pharmacokinetics and Drug Metabolism 1325 Efficacy and Safety 1346 Syntheses 1357 The Future 1378 References 138Chapter 8 Venetoclax (Venclexta): A BCL-2 Antagonist for Treating Chronic Lymphocytic Leukemia 143 1 Background 1432 Pharmacology 1443 Structure–Activity Relationship (SAR) 1474 Pharmacokinetics and Drug Metabolism 1535 Efficacy and Safety 1546 Syntheses 1557 Summary 1608 References 161Chapter 9 Osimertinib (Tagrisso), A Potent and Selective Third-Generation EGFR Inhibitor for the Treatment of Both Sensitizing and T790M-Resistance Mutations 165 1 Background 1652 Pharmacology 1673 Structure–Activity Relationship (SAR) 1704 Pharmacokinetics and Drug Metabolism 1735 Efficacy and Safety 1746 Syntheses 1757 Summary 1808 References 180Chapter 10 Sotorasib (LUMAKRA), An Irreversible Covalent Inhibitor of KRASG12C 183 1 Background 1832 Pharmacology 1843 Structure–Activity Relationship (SAR) 1864 Pharmacokinetics and Drug Metabolism 1915 Efficacy and Safety 1916 Syntheses 1927 Summary 1968 References 196Chapter 11 Lorlatinib (Lorbrena), An ALK Inhibitor for Treating NSCLC 201 1 Background 2012 Pharmacology 2033 Structure–Activity Relationship (SAR) 2054 Pharmacokinetics and Drug Metabolism 2105 Efficacy and Safety 2116 Syntheses 2137 Summary 2268 References 227Chapter 12 Niraparib (Zejula) A Small Molecule, PARP1/2 Inhibitor for Treating Breast, Ovarian, and Pancreatic Cancers 2312 Pharmacology 2353 Structure–Activity Relationship (SAR) 2384 Pharmacokinetics and Drug Metabolism 2435 Efficacy and Safety 2436 Syntheses 2447 Summary 2488 References 248Chapter 13 Selinexor (Xpovio), An XPO1 Inhibitor and a New Class of Therapeutics for Treating Multiple Myeloma 2531 Exportin1 (XPO1) 2532 Overview of Multiple Myeloma 2553 Development of Selinexor 2564 Pharmacology and Mechanism 2575 Pharmacokinetics, Pharmacodynamics and Drug Metabolism 2586 Efficacy and Safety 2597 Syntheses 2598 Summary and Future 2629 References 262Part III Cns Drugs 265Chapter 14 Sage 217 (Zuranolone) for Treating Major of Depressive Disorder2671 Background 2672 Pharmacology 2703 Structure–Activity Relationship (SAR) 2724 Pharmacokinetics and Drug Metabolism 2795 Efficacy and Safety 2806 Syntheses 2817 Summary 2828 References 283Chapter 15 Risdiplam (Evrysdi), A Small Molecule, SMN2-directed RNA Splicing Modifier for Treating Spinal Muscular Atrophy 2871 Background 2872 Pharmacology 2893 Structure–Activity Relationship (SAR) 2904 Pharmacokinetics and Drug Metabolism 2975 Efficacy and Safety 2976 Syntheses 2987 Summary 3008 References 301Part IV Miscellaneous Drugs 305Chapter 16 Esaxerenone (Minnebro), An Oral, Non-steroidal, Selective Mineralocorticoid Receptor Blocker for the Treatment of Essential Hypertension3071 Background 3072 Pharmacology 3103 Structure–Activity Relationship (SAR) 3114 Pharmacokinetics and Drug Metabolism 3135 Efficacy and Safety 3156 Syntheses 3167 Summary 3208 References 321Chapter 17 Voclosporin (Lupkynis), A Macrocyclic Peptide Inhibitor of Calcineurin for the Treatment of Lupus Nephritis 3231 Background 3232 Pharmacology 3263 Structure–Activity Relationship (SAR) 3264 Pharmacokinetics and Drug Metabolism 3295 Efficacy and Safety 3316 Syntheses 3337 References 336Chapter 18 Computational-Aided Drug Design 3391 Background 3392 Structure-based Drug Design (SBDD) 3413 Ligand-based Drug Design (LBDD) 3524 Summary 3615 References 362Index 373
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