Lavoisier S.A.S.
14 rue de Provigny
94236 Cachan cedex
FRANCE

Heures d'ouverture 08h30-12h30/13h30-17h30
Tél.: +33 (0)1 47 40 67 00
Fax: +33 (0)1 47 40 67 02


Url canonique : www.lavoisier.fr/livre/sciences-de-la-vie/successful-drug-discovery/fischer/descriptif_3091068
Url courte ou permalien : www.lavoisier.fr/livre/notice.asp?ouvrage=3091068

Successful Drug Discovery, Volume 1

Langue : Anglais
Couverture de l’ouvrage Successful Drug Discovery, Volume 1
The first volume of the book series "Successful Drug Discovery" is focusing on new drug discoveries during the last decade, from established drugs to recently introduced drugs of all kinds: small-molecule-, peptide-, and protein-based drugs.
The role of serendipity is analyzed in some very successful drugs where the research targets of the lead molecule and the drug are different. Phenotypic and target-based drug discovery approaches are discussed from the viewpoint of pioneer drugs and analogues.
This volume gives an excellent overview of insulin analogues including a discussion of the properties of rapid-acting and long-acting formulations of this important hormone.
The major part of the book is devoted to case histories of new drug discoveries described by their key inventors. Eight case histories range across many therapeutic fields.
The goal of this book series is to help the participants of the drug research community with a reference book series and to support teaching in medicinal chemistry with case histories and review articles of new drugs.

Preface XIII

List of Contributors XVII

Part I General Aspects 1

1 Serendipitous Target-Based Drug Discoveries 3
Janos Fischer and David P. Rotella

1.1 Introduction 3

1.2 Recent Examples of Target-Based Drug Discovery 4

1.3 Serendipitous Target-Based Drug Discoveries 7

1.4 Drospirenone (Contraceptive with Anti-aldosterone Activity) 7

1.5 Escitalopram (Selective Serotonin Reuptake Inhibitor Antidepressant) 9

1.6 Ezetimibe (Inhibitor of Cholesterol Absorption) 11

1.7 Lamotrigine (Discovery of a Standalone Drug for the Treatment of Epilepsy) 13

1.8 Omeprazole (Proton Pump Inhibitor Acid-Suppressive Agent) 15

1.9 Outlook 17

Acknowledgments 17

List of Abbreviations 17

References 18

2 Drug Discoveries and Molecular Mechanism of Action 19
David C. Swinney

2.1 Introduction 19

2.2 Mechanistic Paradox 19

2.3 Molecular Mechanism of Action 20

2.4 How MMOAs were Discovered 25

2.5 Case Study: Artemisinin 30

2.6 Summary 31

List of Abbreviations 32

References 32

Part II Drug Class 35

3 Insulin Analogs – Improving the Therapy of Diabetes 37
John M. Beals

3.1 Introduction 37

3.2 Pharmacology and Insulin Analogs 38

3.3 Chemical Description 39

3.4 Rapid-Acting Insulin Analogs (Prandial or Bolus Insulin) 41

3.5 Long-Acting Insulin Analog Formulations (Basal Insulin) 48

3.6 Conclusions and Future Considerations 54

List of Abbreviations 55

References 55

Part III Case Histories 61

4 The Discovery of Stendra™(Avanafil) for the Treatment of Erectile Dysfunction 63
Koichiro Yamada, Toshiaki Sakamoto, Kenji Omori, and Kohei Kikkawa

4.1 Introduction 63

4.2 Discovery of Avanafil 65

4.4 Clinical Studies of Avanafil 81

4.5 Conclusion 83

List of Abbreviations 83

References 83

5 Dapagliflozin, A Selective SGLT2 Inhibitor for Treatment of Diabetes 87
William N.Washburn

5.1 Introduction 87

5.2 Role of SGLT2 Transporters in Renal Function 88

5.3 O-Glucoside SGLT2 Inhibitors 89

5.4 m-Diarylmethane C-Glucosides 97

5.5 Profiling Studies with Dapagliflozin 105

5.6 Clinical Studies with Dapagliflozin 108

5.7 Summary 108

List of Abbreviations 109

References 110

6 Elvitegravir, A New HIV-1 Integrase Inhibitor for Antiretroviral Therapy 113
Hisashi Shinkai

6.1 Introduction 113

6.2 Discovery of Elvitegravir 114

6.3 Conclusion 121

List of Abbreviations 123

References 123

7 Discovery of Linagliptin for the Treatment of Type 2 Diabetes Mellitus 129
Matthias Eckhardt, Thomas Klein, Herbert Nar, and Sandra Thiemann

7.1 Introduction 129

7.2 Discovery of Linagliptin – HighThroughput Screening Hit Optimization 130

7.3 Rationalization of DPP-4 Inhibition Potency by Crystal Structure Analysis and Studies of Binding Kinetics 139

7.4 Basic Physicochemical, Pharmacological, and Kinetic Characteristics 141

7.5 Preclinical Studies 143

7.6 Clinical Studies 146

7.7 Conclusion 151

List of Abbreviations 151

References 152

8 The Discovery of Alimta (Pemetrexed) 157
Edward C. Taylor

List of Abbreviations 175

References 176

9 Perampanel: A Novel, Noncompetitive AMPA Receptor Antagonist for the Treatment of Epilepsy 181
Shigeki Hibi

9.1 Introduction 181

9.2 Seeds Identification by High Throughput Screening (HTS) Assays 183

9.3 Structure and Activity Relationship (SAR) Study Starting from the Unique Structure of Seed Compounds 184

9.4 Pharmacological Properties of Perampanel; Selection for Clinical Development 187

9.5 Clinical Development of Perampanel 189

9.6 Conclusion 190

List of Abbreviations 190

References 191

10 Discovery and Development of Telaprevir (Incivek™) – A Protease Inhibitor to Treat Hepatitis C Infection 195
Bhisetti G. Rao, Mark A. Murcko, Mark J. Tebbe, and Ann D. Kwong

10.1 Introduction 195

10.2 Discussion 197

10.3 Summary 207

List of Abbreviations 208

References 209

11 Antibody–Drug Conjugates: Design and Development of Trastuzumab Emtansine (T-DM1) 213
Sandhya Girish, Gail D. Lewis Phillips, Fredric S. Jacobson, Jagath R. Junutula, and Ellie Guardino

11.1 Introduction 213

11.2 Molecular Design of T-DM1 214

11.3 Strategies for Bioanalysis 216

11.4 Strategies for Chemistry and Manufacturing Control 218

11.5 Nonclinical Development 219

11.6 Clinical Pharmacology 220

11.7 Clinical Trials and Approval 222

11.8 Summary 224

List of Abbreviations 225

References 226

Index 231

Janos Fischer is a Senior Research Scientist at Richter Plc., Budapest, Hungary. He received his MSc and PhD degrees in organic chemistry from the Eotvos University of Budapest under Professor A. Kucsman. Between 1976 and 1978, he was a Humboldt Fellow at the University of Bonn under Professor W. Steglich. He has worked at Richter Plc. since 1981 where he participated in the research and development of leading cardiovascular drugs in Hungary. He is the author of some 100 patents and scientific publications. In 2004, he was elected as a Titular member of the Chemistry and Human Health Division of IUPAC. He received an honorary professorship at the Technical University of Budapest.

David Rotella is the Margaret and Herman Sokol Professor of Medicinal Chemistry at Montclair State University. He earned a B.S. Pharm. degree at the University of Pittsburgh (1981) and a Ph.D. (1985) at The Ohio State University with Donald. T. Witiak. After postdoctoral studies in organic chemistry at Penn State University with Ken S. Feldman, he became an assistant professor at the University of Mississippi. Before accepting his current position he worked at Cephalon, Bristol-Myers, Lexicon and Wyeth where he was involved in neurodegeneration, schizophrenia, cardiovascular and metabolic disease drug discovery projects.

Date de parution :

Ouvrage de 256 p.

17.5x25.2 cm

Disponible chez l'éditeur (délai d'approvisionnement : 14 jours).

156,31 €

Ajouter au panier