Chemistry and Pharmacology of Drug Discovery

1. Auflage 2024
ISBN: 978-1-394-22512-5
Verlag: Wiley

Buch, Englisch, 432 Seiten, Gewicht: 454 g

Autoren/Hrsg.

Li, Jie Jack

Fachgebiete

• Naturwissenschaften Chemie Chemie Allgemein Pharmazeutische Chemie, Medizinische Chemie
• Naturwissenschaften Chemie Organische Chemie
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizinische Fachgebiete Pharmakologie, Toxikologie

Inhaltsverzeichnis

Preface xi

Contributing Authors xiii

Section I. Drugs Treating Infectious Diseases 1

Chapter 1. Nirmatrelvir (Paxlovid with Ritonavir): A 3-Chymotrypsin-like Protease Inhibitor for Treating SARS-CoV-2 Infection 3
Jie Jack li

1 Background 4

2 Pharmacology 5

2.1 The Coronavirus 5

2.2 The 3CL Protease 6

2.3 The Mechanism of Action of Nirmatrelvir 9

3 Structure–Activity Relationship (SAR) 10

3.1 The Pyrrolidone Substituent at P1 10

3.2 Dimethylcyclopropylproline at P2 11

3.3 The Nitrile Warhead at P1’ 13

3.4 Lead Optimization 14

4 Pharmacokinetics and Drug Metabolism 17

4.1 Pharmacokinetics of Nirmatrelvir 17

4.2 Metabolism of Nirmatrelvir 17

5 Efficacy and Safety 18

6 Synthesis 19

6.1 Scale-up Route 19

6.2 Manufacturing Route 23

7 Summary 24

References 25

Chapter 2. Doravirine (Pifeltro): A Third-generation Nonnucleoside Reverse Transcriptase Inhibitor as a Treatment of HIV-1 Infection 29
Jie Jack li

1 Background 30

2 Pharmacology 32

3 Structure–Activity Relationship (SAR) 38

4 Pharmacokinetics and Drug Metabolism 43

5 Efficacy and Safety 45

6 Synthesis 46

7 Summary 49

References 49

Chapter 3. Cabotegravir (Vocabria): An HIV Integrase Strand Transfer Inhibitor for Treating HIV Infection 53
Jie Jack li

1 Background 54

2 Pharmacology 54

2.1 HIV Integrase 54

2.2 First-Generation HIV Integrase Inhibitors 58

2.3 Second-Generation HIV Integrase Inhibitors 61

2.4 Integrase–LEDGF/p75 Allosteric Inhibitors 63

3 Structure–Activity Relationship (SAR) 65

4 Pharmacokinetics and Drug Metabolism 68

5 Efficacy and Safety 69

6 Synthesis 70

7 Summary 74

References 74

Chapter 4. Lenacapavir (Sunlenca): A Long-acting HIV-1 Capsid Pro

Über Autor(innen)

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, many published by Wiley.