Case Studies in Modern Drug Discovery and Development
(Sprache: Englisch)
Learn why some drug discovery and development efforts succeed . . . and others fail
Written by international experts in drug discovery and development, this book sets forth carefully researched and analyzed case studies of both successful and failed drug...
Written by international experts in drug discovery and development, this book sets forth carefully researched and analyzed case studies of both successful and failed drug...
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Klappentext zu „Case Studies in Modern Drug Discovery and Development “
Learn why some drug discovery and development efforts succeed . . . and others failWritten by international experts in drug discovery and development, this book sets forth carefully researched and analyzed case studies of both successful and failed drug discovery and development efforts, enabling medicinal chemists and pharmaceutical scientists to learn from actual examples. Each case study focuses on a particular drug and therapeutic target, guiding readers through the drug discovery and development process, including drug design rationale, structure-activity relationships, pharmacology, drug metabolism, biology, and clinical studies.
Case Studies in Modern Drug Discovery and Development begins with an introductory chapter that puts into perspective the underlying issues facing the pharmaceutical industry and provides insight into future research opportunities. Next, there are fourteen detailed case studies, examining:
All phases of drug discovery and development from initial idea to commercialization
Some of today's most important and life-saving medications
Drugs designed for different therapeutic areas such as cardiovascular disease, infection, inflammation, cancer, metabolic syndrome, and allergies
Examples of prodrugs and inhaled drugs
Reasons why certain drugs failed to advance to market despite major research investments
Each chapter ends with a list of references leading to the primary literature. There are also plenty of tables and illustrations to help readers fully understand key concepts, processes, and technologies.
Improving the success rate of the drug discovery and development process is paramount to the pharmaceutical industry. With this book as their guide, readers can learn from both successful and unsuccessful efforts in order to apply tested and proven science and technologies that increase the probability of success for new drug discovery and development projects.
Inhaltsverzeichnis zu „Case Studies in Modern Drug Discovery and Development “
PREFACE xvCONTRIBUTORS xvii
CHAPTER 1 INTRODUCTION: DRUG DISCOVERY IN DIFFICULT TIMES 1
Malcolm MacCoss
CHAPTER 2 DISCOVERY AND DEVELOPMENT OF THE DPP-4 INHIBITOR JANUVIA(TM) (SITA-GLIPTIN) 10
Emma R. Parmee, Ranabir SinhaRoy, Feng Xu, Jeffrey C. Givand, and Lawrence A. Rosen
2.1 Introduction 10
2.2 DPP-4 Inhibition as a Therapy for Type 2 Diabetes: Identification of Key Determinants for Efficacy and Safety 10
2.3 Medicinal Chemistry Program 20
2.4 Synthetic and Manufacturing Routes to Sitagliptin 27
2.5 Drug Product Development 33
2.6 Clinical Studies 36
2.7 Summary 39
References 39
CHAPTER 3 OLMESARTAN MEDOXOMIL: AN ANGIOTENSIN II RECEPTOR BLOCKER 45
Hiroaki Yanagisawa, Hiroyuki Koike, and Shin-ichiro Miura
3.1 Background 45
3.2 The Discovery of Olmesartan Medoxomil (Benicar) 47
3.3 Characteristics of Olmesartan 53
3.4 Binding Sites of Omlersartan to the AT1 Receptor and Its Inverse Agonoist Activity 56
3.5 Practical Preparation of Olmesartan Medoxomil 58
3.6 Preclinical Studies 58
3.7 Clinical Studies 62
3.8 Conclusion 63
References 64
CHAPTER 4 DISCOVERY OF HETEROCYCLIC PHOSPHONIC ACIDS AS NOVELAMPMIMICS THAT ARE POTENT AND SELECTIVE FRUCTOSE-1,6-BISPHOSPHATASE INHIBITORS AND ELICIT POTENT GLUCOSE-LOWERING EFFECTS IN DIABETIC ANIMALS AND HUMANS 67
Qun Dang and Mark D. Erion
4.1 Introduction 67
4.2 The Discovery of MB06322 69
4.3 Pharmacokinetic Studies of MB06322 82
4.4 Synthetic Routes to MB06322 83
4.5 Clinical Studies of MB06322 83
4.6 Summary 84
References 85
CHAPTER 5 SETTING THE PARADIGM OF TARGETED DRUGS FOR THE TREATMENT OF CANCER: IMATINIB AND NILOTINIB, THERAPIES FOR CHRONIC MYELOGENOUS LEUKEMIA 88
Paul W. Manley and Jürg Zimmermann
5.1 Introduction 88
5.2
... mehr
Chronic Myelogenous Leukemia (CML) and Early Treatment of the Disease 89
5.3 Imatinib: A Treatment for Chronic Myelogenous Leukemia (CML) 92
5.4 The Need for New Inhibitorts of BCR-ABL1 and Development of Nilotinib 94
5.5 Conclusion 99
References 100
CHAPTER 6 AMRUBICIN, A COMPLETELY SYNTHETIC 9-AMINOANTHRACYCLINE FOR EXTENSIVE-DISEASE SMALL-CELL LUNG CANCER 103
Mitsuharu Hanada
6.1 Introduction 103
6.2 The Discovery of Amrubicin: The First Completely Synthetic Anthracycline 106
6.3 Toxicological Profile of Amrubicin 107
6.4 DNA Topoisomerase II Inhibition and Apoptosis Induction by Amrubicin 110
6.5 Amrubicin Metabolism: The Discovery of Amrubicinol 113
6.6 Improved Usage of Amrubicin 116
6.7 Clinical Trials 118
6.8 Conclusions 122
References 123
CHAPTER 7 THE DISCOVERY OF DUAL IGF-1R AND IR INHIBITOR FQIT FOR THE TREATMENT OF CANCER 127
Meizhong Jin, Elizabeth Buck, and Mark J. Mulvihill
7.1 Biological Rational for Targeting the IGF-1R/IR Pathway for Anti-Cancer Therapy 127
7.2 Discovery Of OSI-906 128
7.3 OSI-906 Back Up Efforts 131
7.4 The Discovery Of FQIT 131
7.5 In Vitro Profile of FQIT 140
7.6 Pharmacokinetic Properties of FQIT 144
7.7 In Vivo Profile of FQIT 146
7.8 Safety Assessment and Selectivity Profile of FQIT 148
7.9 Summary 150
Acknowledgments 151
References 151
CHAPTER 8 DISCOVERY AND DEVELOPMENT OF MONTELUKAST (SINGULAIR(r)) 154
Robert N. Young
8.1 Introduction 154
8.2 Drug Development Strategies 158
8.3 LTD4 Antagonis
5.3 Imatinib: A Treatment for Chronic Myelogenous Leukemia (CML) 92
5.4 The Need for New Inhibitorts of BCR-ABL1 and Development of Nilotinib 94
5.5 Conclusion 99
References 100
CHAPTER 6 AMRUBICIN, A COMPLETELY SYNTHETIC 9-AMINOANTHRACYCLINE FOR EXTENSIVE-DISEASE SMALL-CELL LUNG CANCER 103
Mitsuharu Hanada
6.1 Introduction 103
6.2 The Discovery of Amrubicin: The First Completely Synthetic Anthracycline 106
6.3 Toxicological Profile of Amrubicin 107
6.4 DNA Topoisomerase II Inhibition and Apoptosis Induction by Amrubicin 110
6.5 Amrubicin Metabolism: The Discovery of Amrubicinol 113
6.6 Improved Usage of Amrubicin 116
6.7 Clinical Trials 118
6.8 Conclusions 122
References 123
CHAPTER 7 THE DISCOVERY OF DUAL IGF-1R AND IR INHIBITOR FQIT FOR THE TREATMENT OF CANCER 127
Meizhong Jin, Elizabeth Buck, and Mark J. Mulvihill
7.1 Biological Rational for Targeting the IGF-1R/IR Pathway for Anti-Cancer Therapy 127
7.2 Discovery Of OSI-906 128
7.3 OSI-906 Back Up Efforts 131
7.4 The Discovery Of FQIT 131
7.5 In Vitro Profile of FQIT 140
7.6 Pharmacokinetic Properties of FQIT 144
7.7 In Vivo Profile of FQIT 146
7.8 Safety Assessment and Selectivity Profile of FQIT 148
7.9 Summary 150
Acknowledgments 151
References 151
CHAPTER 8 DISCOVERY AND DEVELOPMENT OF MONTELUKAST (SINGULAIR(r)) 154
Robert N. Young
8.1 Introduction 154
8.2 Drug Development Strategies 158
8.3 LTD4 Antagonis
... weniger
Autoren-Porträt von Xianhai Huang, Robert G. Aslanian
Xianhai Huang, PhD, is a Principal Scientist at Merck Research Laboratories. Dr. Huang is the inventor or co-inventor on more than forty patents and patent applications. As a mentor in the Schering-Plough chemistry postdoctoral program, Dr. Huang and his group discovered novel synthetic applications of (diacetoxyiodo) benzene and successfully applied the methodology to the total synthesis of psymberin, an antitumor natural product.Robert G. Aslanian, PhD, is an adjunct professor of chemistry at William Paterson University and was formerly a Senior Director of Medicinal Chemistry with the Schering-Plough Research Institute and Merck Research Laboratories. Dr. Aslanian has over twenty-five years of experience in the pharmaceutical industry. He is co-inventor on thirty-eight U.S. patents and coauthor on sixty-seven scientific articles and reviews.
Bibliographische Angaben
- Autoren: Xianhai Huang , Robert G. Aslanian
- 2012, 1. Auflage, 480 Seiten, mit Abbildungen, Maße: 18,3 x 26 cm, Gebunden, Englisch
- Verlag: Wiley & Sons
- ISBN-10: 0470601817
- ISBN-13: 9780470601815
- Erscheinungsdatum: 22.06.2012
Sprache:
Englisch
Rezension zu „Case Studies in Modern Drug Discovery and Development “
"This book will enrich the collection of medicinal chemists or pharmacologists involved in active drug discovery research, as well as students with a passion for pursuing a career in drug discovery." ("Doody's", 22 February 2013) "A well-made glossary is available in the appendix, which defines the dozens of terms that a medicinal chemist will encounter in his/her career. . . This book demonstrates yet again the need for new, better medicines and the reasons for the high cost of drug research. An enjoyable read!." ("ChemMedChem", 1 January 2013)
Pressezitat
"This book will enrich the collection of medicinal chemists or pharmacologists involved in active drug discovery research, as well as students with a passion for pursuing a career in drug discovery." ( Doody's , 22 February 2013)"A well-made glossary is available in the appendix, which defines the dozens of terms that a medicinal chemist will encounter in his/her career. . . This book demonstrates yet again the need for new, better medicines and the reasons for the high cost of drug research. An enjoyable read!." ( ChemMedChem , 1 January 2013)
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