Current Drug Synthesis

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.

List of contents

Preface xi
 
Contributing Authors xiii
 
Part I Infectious Disease Drugs 1
 
Chapter 1 Relebactam (Recarbrio), A ß-Lactamase Inhibitor for the Treatment of cIAI/cUTI/HABP/ VABP 3
 
1 Background 3
 
2 Pharmacology 5
 
3 Structure-Activity Relationship (SAR) 6
 
4 Pharmacokinetics and Drug Metabolism 9
 
5 Efficacy and Safety 10
 
6 Syntheses 10
 
7 Summary 14
 
8 References 14
 
Chapter 2 Vaborbactam (in Combination with Meropenem as Vabomere), a Non-ß-Lactam ß-Lactamase Inhibitor for Treatment of Complicated Urinary Tract Infections and Pyelonephritis 17
 
1 Background 17
 
2 Discovery Medicinal Chemistry 21
 
3 Vaborbactam/Vabomere Clinical Trials 27
 
4 Vaborbactam Medicinal Chemistry Synthesis 29
 
5 Vaborbactam Process Chemistry Synthesis 30
 
6 Conclusions 37
 
7 References 38
 
Chapter 3 Baloxavir Marboxil (Xofluza), A Cap-Dependent Endonuclease Inhibitor for Treating Influenza 41
 
1 Background 41
 
2 Mechanism of Action 43
 
3 Structure-Activity Relationship 45
 
4 Pharmacokinetics and Drug Metabolism 49
 
5 Efficacy and Safety 50
 
6 Syntheses 50
 
7 Summary 54
 
8 References 54
 
Chapter 4 Process Chemistry Development of the HIV Protease Inhibitor Drug Kaletra: A Mixture of Ritonavir and Lopinavir 57
 
1 Background 58
 
2 Ritonavir Portion of Kaletra Synthesis 58
 
3 Discovery Synthesis of the Ritonavir Core 60
 
4 Discovery Synthesis of Ritonavir Wing Pieces 63
 
5 Large-Scale Process Chemistry Synthesis of the Ritonavir Core 65
 
6 Large-Scale Syntheses of the 5-Hydroxymethyl Thiazole Wing Portion 69
 
7 The Large-Scale Coupling of the Thiazole Wing Pieces to the Core 70
 
8 Lopinavir Portion of Kaletra-- Discovery Synthesis and Process Development 72
 
9 Discovery Synthesis of Lopinavir 73
 
10 Discovery Synthesis of Wing Pieces 74
 
11 Process Improvements to the Wing Pieces 76
 
12 Optimization of Lopinavir Synthesis with Intermediates 78
 
13 Conclusions 81
 
14 References 81
 
Chapter 5 Eravacycline (Xerava), A Novel and Completely Synthetic Fluorocycline Antibiotic 85
 
1 Background 85
 
2 Pharmacology 89
 
3 Structure-Activity Relationship (SAR) 91
 
4 Pharmacokinetics and Drug Metabolism 93
 
5 Efficacy and Safety 93
 
6 Syntheses 93
 
7 Summary 98
 
8 References 99
 
Chapter 6 Albuvirtide (Aikening), A gp41 Analog as an HIV-1 Fusion Inhibitor 101
 
1 Background 101
 
2 Pharmacology 102
 
3 Structure-Activity Relationship (SAR) 106
 
4 Pharmacokinetics and Drug Metabolism 107
 
5 Efficacy and Safety 110
 
6 Syntheses 112
 
7 Summary 114
 
8 References 115
 
Part II Cancer Drugs 119
 
Chapter 7 Darolutamide (Nubeqa): An Androgen Receptor Antagonist for Treating Nonmetastatic, Castration-Resistant 121
 
1 Background 121
 
2 Pharmacology 124
 
3 Structure-Activity Relationship (SAR) 126
 
4 Pharmacokinetics and Drug Metabolism 132
 
5 Efficacy and Safety 134
 
6 Syntheses 135
 
7 The Future 137
 
8 References 138
 
Chapter 8 Venetoclax (Venclexta): A BCL-2 Antagonist for Treating Chronic Lymphocytic Leukemia 143
 
1 Background 143
 
2 Pharmacology 144
 
3 Structure-Activity Relationship (SAR) 147
 
4 Pharmacokinetics and Drug Metabolism 153
 
5 Efficacy and Safety 154
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About the author

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.

Summary

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.

Product details

• Authors: Jie Jack Li, JJ Li
• Assisted by: Jie Jack Li (Editor), Jie Jack Li (Editor), Li Jie Jack (Editor)
• Publisher: Wiley, John and Sons Ltd
• Languages: English
• Product format: Hardback
• Released: 17.11.2022
• EAN: 9781119847250
• ISBN: 978-1-119-84725-0
• No. of pages: 400
• Series: Wiley Series on Drug Synthesis
• Subjects: Natural sciences, medicine, IT, technology > Chemistry > Organic chemistry; Chemie, Organische Chemie, Medizin, Pharmakologie, ORGANIC CHEMISTRY, chemistry, Pharmacology & Pharmaceutical Medicine, Pharmakologie u. Pharmazeutische Medizin, Medical Science, Pharmaceutical & Medicinal Chemistry, Pharmazeutische u. Medizinische Chemie, Arzneimittelentwicklung