Current Drug Synthesis

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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 marboxil
  • In-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.

Author(s): Jie Jack Li
Series: Wiley Series on Drug Synthesis
Publisher: Wiley
Year: 2022

Language: English
Pages: 400
City: Hoboken

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