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Informationen zum Autor 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. Klappentext Case studies of 20 successful FDA-approved drugs, from biological rationale to clinical efficacy studies and state-of-the-art applications Chemistry and Pharmacology of Drug Discovery illustrates how chemistry, biology, pharmacokinetics, and a host of disciplines come together to produce successful medicines, discussing a total of 20 drugs that are all FDA-approved post 2021--some of which are first-in-class and revolutionary. The four sections in this book cover Infectious Disease, Cancer Drugs, CNS Drugs, and Miscellaneous Drugs. Each chapter covers background material on the drug class and/or disease indication and key aspects relevant to the discovery of the drug, including structure-activity relationships, pharmacokinetics, drug metabolism, efficacy, and safety. This book is contributed to by various veterans and well-known experts in medical chemistry, many of whom discovered the drugs they reviewed, leading to tremendous quality and depth of insight. Some of the drugs covered in Chemistry and Pharmacology of Drug Discovery include: Nirmatrelvir (Paxlovid with Ritonavir), a 3-chymotrypsin-like protease inhibitor for treating SARS-CoV-2 infectionDoravirine (Pifeltro), a third-generation non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infectionOteseconazole (Vivjoa), a CYP51 inhibitor for treating recurrent vulvovaginal candidiasis, and Rimegepant (Nurtec ODT), a CGRP antagonist for treating migraineCiprofol (Cipepofol), a ?-Aminobutyric acid receptor agonist for induction of anesthesia, and Ozanimod (Zeposia), an S1P receptor antagonist for treating multiple sclerosisDeucravacitinib (Sotyktu), a first-in-class deuterated TYK2 inhibitor for the treatment of plaque psoriasis Chemistry and Pharmacology of Drug Discovery serves as an excellent and highly authoritative learning resource for medicinal, organic, synthetic, and process chemists as well as research scientists in lead optimization and process development. 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 Integ...
