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Chemistry and Pharmacology of Drug Discovery -

Chemistry and Pharmacology of Drug Discovery

Jie Jack Li (Herausgeber)

Buch | Hardcover
432 Seiten
2024
John Wiley & Sons Inc (Verlag)
978-1-394-22512-5 (ISBN)
CHF 269,95 inkl. MwSt
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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 infection
  • Doravirine (Pifeltro), a third-generation non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection
  • Oteseconazole (Vivjoa), a CYP51 inhibitor for treating recurrent vulvovaginal candidiasis, and Rimegepant (Nurtec ODT), a CGRP antagonist for treating migraine
  • Ciprofol (Cipepofol), a γ-Aminobutyric acid receptor agonist for induction of anesthesia, and Ozanimod (Zeposia), an S1P receptor antagonist for treating multiple sclerosis
  • Deucravacitinib (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.

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.

Preface xi

Contributors xiii

 

PART 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   16

 4.1 Pharmacokinetics of Nirmatrelvir   16

 4.2 Metabolism of Nirmatrelvir    16

5 Efficacy and Safety  17

6 Syntheses  18

7 Summary 23

8 References  23

 

Chapter 2. Doravirine (Pifeltro): A Third-generation Non-nucleoside Reverse Transcriptase Inhibitor as a Treatment of HIV-1 Infection  27

Jie Jack Li

1 Background 27

2 Pharmacology  30

3 Structure–Activity Relationship (SAR)   36

4 Pharmacokinetics and Drug Metabolism   40

5 Efficacy and Safety  42

6 Syntheses  43

7 Summary 46

8 References  46

 

Chapter 3. Cabotegravir (Vocabria), HIV Integrase Strand Transfer Inhibitor for Treating HIV Infection   51

Jie Jack Li

1 Background 52

2 Pharmacology  52

 2.1 HIV Integrase  52

 2.2 First-Generation HIV Integrase Inhibitors  55

 2.3 Second-Generation HIV Integrase Inhibitors  59

 2.4 Integrase–LEDGF/p75 Allosteric Inhibitors  61

3 Structure–Activity Relationship (SAR)   63

4 Pharmacokinetics and Drug Metabolism   65

5 Efficacy and Safety  66

6 Syntheses  67

7 Summary 71

8 References  72

 

Chapter 4. Lenacapavir (Sunlenca): A Long-acting HIV-1 Capsid Protein Inhibitor for Treating HIV Infection   75

Jie Jack Li

1 Background 76

2 Pharmacology  77

3 Structure–Activity Relationship (SAR)   83

4 Pharmacokinetics and Drug Metabolism   87

5 Efficacy and Safety  88

6 Synthesis  88

7 Summary 93

8 References  93

 

Chapter 5. Fostemsavir (Rukobia), HIV-1 Attachment Inhibitor   95

Tao Wang and Xiang Li

1 Background 95

2 Pharmacology  97

3 Structure–Activity Relationship (SAR)   98

4 Pharmacokinetics and Drug Metabolism   104

5 Efficacy and Safety  107

6 Syntheses  108

7 Summary 114

8 References  115

 

Chapter 6. Oteseconazole (Vivjoa), A CYP51 Inhibitor for

Treating Recurrent Vulvovaginal Candidiasis   119

Charles Lail and Timothy Hagen

1 Background 119

2 Pharmacology  128

3 Structure–Activity Relationship (SAR)   130

4 Pharmacokinetics and Drug Metabolism   133

5 Efficacy and Safety  134

6 Syntheses  135

7 Summary 139

8 References  139

 

PART II.  CANCER DRUGS     145

 

Chapter 7. Futibatinib (Lytgobi), A Selective Irreversible FGFR1—4 Inhibitor 147

Faridoon and Zhang Guiping

1 Background 147

2 Pharmacology  150

3 Structure–Activity Relationship (SAR)   156

4 Pharmacokinetics and Drug Metabolism   156

5 Efficacy and Safety  156

6 Syntheses  157

7 Summary 161

8 References  161

 

Chapter 8. Pacritinib (Vonjo), A Dual JAK2/IRAK1 Inhibitor for Treating Myelofibrosis  163

Faridoon and Zhang Guiping

1 Background 163

2 Pharmacology  165

3 Structure–Activity Relationship (SAR)   168

4 Pharmacokinetics and Drug Metabolism   172

5 Efficacy and Safety  173

6 Syntheses  175

7 Summary 179

8 References  179

 

Chapter 9. Tucatinib (Tukysa), An Oral, Selective HER2 Inhibitor for the Treatment of HER2-positive Solid Tumors  183

Fengtao Zhou and Ke Ding

1 Background 184

2 Pharmacology  185

3 Pharmacokinetics and Drug Metabolism   186

4 Efficacy and Safety  187

5 Syntheses  188

6 Summary 192

7 References  193

 

 

Chapter 10. Tazemetostat (Tazverik), An EZH2 Inhibitor for Treatment of Epithelioid Sarcoma and Follicular Lymphoma 195

Ruheng Zhao and Timothy A. Cernak

1 Background 195

2 Pharmacology  196

3 Structure–Activity Relationship (SAR)   198

4 Pharmacokinetics and Drug Metabolism   203

5 Efficacy and Safety  204

6 Syntheses  205

7 Summary 208

8 References  208

 

PART III.  CNS DRUGS  211

 

Chapter 11. Ozanimod (Zeposia), An S1P receptor Antagonist for Treating Multiple Sclerosis  213

Shaohui Yu and Xi Wang

1 Background 213

2 Pharmacology  216

3 Pharmacokinetics and Drug Metabolism   222

4 Structure–Activity Relationship (SAR)   224

5 Efficacy and Safety  229

6 Syntheses  232

7 Summary 235

8 References  236

 

Chapter 12. Ciprofol (Cipepofol): A γ-Aminobutyric Acid Receptor Agonist for Induction of Anesthesia    245

Ji Zhang and Dao-Qian Chen

1 Background 246

2 Pharmacology  249

3 Structure–Activity Relationship (SAR)   250

4 Pharmacokinetics and Drug Metabolism   255

5 Efficacy and Safety  257

6 Syntheses  258

7 Summary 262

8 References  262

 

Chapter 13. Rimegepant (Nurtec ODT), a CGRP Antagonist for Treating Migraine  267

Guanglin Luo and Yuqi Lavender Zha

1 Background 268

2 Pharmacology  270

3 Structure–Activity Relationship (SAR)   273

4 Pharmacokinetics and Drug Metabolism   278

5 Efficacy and Safety  279

6 Syntheses  281

7 Summary 284

8 References  285

 

Chapter 14. Daridorexant (Quviviq), An Antagonist of Orexin Receptors for Treating Insomnia     291

Dexi Yang

1 Background 291

2 Pharmacology  296

3 Structure–Activity Relationship (SAR)   297

4 Pharmacokinetics and Drug Metabolism   303

5 Efficacy and Safety  304

6 Syntheses  306

7 Summary 310

8 References  310

 

 

PART IV.  ANTI-INFLAMMATORY DRUGS   315

 

Chapter 15. Deucravacitinib (Sotyktu): A First-in-class Deuterated TYK2 Inhibitor for the Treatment of Plaque Psoriasis  317

Daljit Matharu

1 Background 317

2 Pharmacology  322

3 Structure–Activity Relationship (SAR)   323

4 Pharmacokinetics and Drug Metabolism   333

5 Efficacy and Safety  334

6 Syntheses  336

7 Summary 348

8 References  349

 

PART V.  MISCELLANEOUS DRUGS   353

 

Chapter 16. Bremelanotide (Vyleesi), A Melanocortin Receptor Agonist for Treating Female Hypoactive Sexual Desire Disorder   355

Yan Wang

1 Background 355

2 Pharmacology  358

3 Structure–Activity Relationship (SAR)   360

4 Pharmacokinetics and Drug Metabolism   362

5 Efficacy and Safety  362

6 Syntheses  363

7 Summary 368

8 References  368

 

Chapter 17. Odevixibat (Bylvay), A Selective Inhibitor of the Ileal Bile Acid Transporter  373

Andrew Outlaw and Timothy A. Cernak

1 Background 374

2 Pharmacology  376

3 Structure–Activity Relationship (SAR)   380

4 Pharmacokinetics and Drug Metabolism   384

5 Efficacy and Safety  384

6 Syntheses  385

7 Summary 388

8 References  389

 

Index  393

Erscheinungsdatum
Verlagsort New York
Sprache englisch
Gewicht 454 g
Einbandart gebunden
Themenwelt Medizin / Pharmazie Medizinische Fachgebiete Pharmakologie / Pharmakotherapie
Naturwissenschaften Biologie Biochemie
Naturwissenschaften Chemie Organische Chemie
ISBN-10 1-394-22512-1 / 1394225121
ISBN-13 978-1-394-22512-5 / 9781394225125
Zustand Neuware
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