成功的药物发现 第3卷 Successful Drug Discovery - Volume 3

基本信息

Format:Hardback 472 pages

Publisher:Wiley-VCH Verlag GmbH

Imprint:Blackwell Verlag GmbH

ISBN:9783527343034

Published:18 Apr 2018

Weight:1043g

Dimensions:244 x 175 (mm)

页面参数仅供参考，具体以实物为准

书籍简介

由于其重点是推出的药物，以至于在任何其他教科书或一般参考书中都没有发现这些药物，这里发现的信息和洞察力使其成为一本真正手册和参考书。

按照该系列前几卷的成功方法，来自工业界和学术界的成功药物的发明者和主要开发者讲述了药物的发现故事，并描述了从一个候选药物分子到上市的药物的有时曲折的路线。所选的11个案例研究描述了药物，涉及许多治疗领域，提供了当今药物发展的代表性截面。在大量数据和化学信息的支持下，当今药物创造者的洞察力和经验使本书成为初级药物化学家可能希望找到的有用的培训手册之一。

国际纯粹与应用化学联盟认可并赞助了这个项目，因为它具有很高的教育价值。

With its focus on drugs so recently introduced that they have yet to be found in any other textbooks or general references, the information and insight found here makes this a genuinely unique handbook and reference.

Following the successful approach of the previous volumes in the series, inventors and primary developers of successful drugs from both industry and academia tell the story of the drug's discovery and describe the sometimes twisted route from the first drug candidate molecule to the final marketed drug. The 11 case studies selected describe recent drugs ranging across many therapeutic fields and provide a representative cross-section of present-day drug developments. Backed by plenty of data and chemical information, the insight and experience of today's top drug creators makes this one of the most useful training manuals that a junior medicinal chemist may hope to find.

The International Union of Pure and Applied Chemistry has endorsed and sponsored this project because of its high educational merit.

作者简介

亚诺什-菲舍尔是匈牙利布达佩斯Richter Plc.公司的高级研究科学家。他在布达佩斯Eotvos大学获得有机化学的硕士和博士学位，师从A. Kucsman教授。1976年至1978年期间，他在波恩大学担任洪堡研究员，师从W. Steglich教授。自1981年起，他在Richter Plc.工作，参与了匈牙利主要心血管药物的研究和开发。他的主要兴趣是基于模拟物的药物发现。他是约100项专利和科学出版物的作者。自2014年以来，他是国际理论化学联合会药物发现和开发小组委员会的主席。他获得了布达佩斯技术大学的荣誉教授职位。

克里斯蒂安-克莱因是苏黎世罗氏创新中心的肿瘤学项目负责人，专门从事基于抗体的癌症免疫疗法和双特异性抗体的发现、验证和临床前开发。在罗氏工作的15年中，他对obinutuzumab的开发和批准、目前处于临床阶段的8种双特异性抗体/免疫细胞因子的临床前开发，以及罗氏的新型专利双特异性抗体平台（如CrossMAb技术）的开发做出了重大贡献。

韦恩-E-柴尔德斯是美国费城天普大学的制药科学副教授。韦恩在范德比尔特大学获得化学学士学位（1979年），在乔治亚大学获得有机化学博士学位（1984年），师从Harold Pinnick。在接受约翰霍普金斯大学医学院塞西尔-罗宾逊博士的实验室的博士后研究员职位之前，他曾在巴克内尔大学担任助理兼职教授。然后他加入惠氏，在许多治疗领域工作，包括精神疾病、中风和阿尔茨海默氏病，以及慢性疼痛的治疗。他在惠氏公司工作了22年，然后于2010年加入天普大学的教师队伍。

János 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. His main interest is analogue based drug discovery. He is the author of some 100 patents and scientific publications. Since 2014 he is Chair of the Subcommittee on Drug Discovery and Development of IUPAC. He received an honorary professorship at the Technical University of Budapest.

Christian Klein is Head of Oncology Programs at the Roche Innovation Center Zurich, specialized in the discovery, validation and preclinical development of antibody based cancer immunotherapies and bispecific antibodies. During his 15 years at Roche he has made major contributions to the development and approval of obinutuzumab, the preclinical development of eight clinical stage bispecific antibodies/immunocytokines that are currently at the clinical stage, as well as the development of Roche's novel proprietary bispecific antibody platforms, e.g., the CrossMAb technology.

Wayne E. Childers is Associate Professor of Pharmaceutical Sciences at Temple University, Philadelphia, USA. Wayne received his BA (1979) degree from Vanderbilt University in chemistry and PhD (1984) in organic chemistry from the University of Georgia under the direction of Harold Pinnick. He served as an assistant adjunct professor at Bucknell University before accepting a position as a postdoctoral fellow at the Johns Hopkins University School of Medicine in the laboratories of Dr. Cecil Robinson. He then joined Wyeth, working in numerous therapeutic areas, including psychiatric diseases, stroke, and Alzheimer's disease, and the treatment of chronic pain. He stayed with Wyeth for 22 years, before joining the faculty of Temple University in 2010.

目录

部分目录，仅供参考

TABLE OF CONTENTS

Preface xvii

Part I General Aspects 1

1 New Trends in Drug Discovery 3

Gerd Schnorrenberg

1.1 Introduction 3

1.1.1 Analysis of New Molecular Entities Approved in 2015 3

1.2 New Trends in NCE Discovery 7

1.3 Enhanced Lead Generation Strategies 7

1.3.1 Analogue Approach 9

1.3.2 High Throughput Screening (HTS) 9

1.3.3 Structure-Based Design 11

1.3.4 Virtual Screening 12

1.3.5 Fragment-Based Lead Discovery 13

1.3.6 Repositioning 14

1.3.7 Additional New Trends in Hit/Lead Generation 15

1.4 Early Assessment of Development Aspects during Drug Discovery 16

1.4.1 DMPK 17

1.4.2 Assessment of Physicochemical Parameters 18

1.4.3 Tolerability Assessment 19

1.5 New Biological Entities (NBEs) 19

1.5.1 Antibody Engineering to Reduce Immunogenicity 23

1.5.2 Progress in Antibody Production and Engineering of Physicochemical Properties 24

1.5.3 Engineering to Improve Efficacy 25

1.5.4 New Formats 26

1.5.4.1 Antibody–Drug Conjugates 26

1.5.4.2 Bispecific Antibodies 28

1.6 General Challenges in Drug Discovery 30

1.7 Summary 31

Acknowledgments 31

List of Abbreviations 31

References 32

2 Patenting Small and Large Pharmaceutical Molecules 41

Uwe Albersmeyer, Ralf Malessa, and Ulrich Storz

2.1 The Role of Patents in the Pharmaceutical Industry 41

2.2 Classification of Active Pharmaceutical Ingredient Grouping 42

2.3 Patentability Criteria and Patentable Embodiments 43

2.3.1 Patent Eligibility and Patentability 43

2.3.2 Patent Eligibility of Molecules 43

2.3.2.1 Small Molecules and Peptides 44

2.3.2.2 Molecules Isolated from Nature 44

2.3.3 Novelty 44

2.3.3.1 Novelty of Molecules that are More or Less Identical to Molecules from the Human Body 46

2.3.4 Inventive Step/Non-Obviousness 47

2.3.5 Patentability Criteria and Patentable Embodiments in Biopharmaceutics 47

2.3.5.1 Different Types of Biopharmaceutics 47

2.3.5.2 Monoclonal Antibodies 48

2.3.5.3 Nucleic Acid-Based Therapeutics 49

2.4 Patent Term Extensions and Adjustments, Supplementary Protection Certificates, and Data Exclusivity in Biopharmaceutics 49

2.4.1 Introduction 49

2.4.2 Patent Lifetime 49

2.4.2.1 Patent Term Adjustment (PTA) 50

2.4.2.2 Patent Term Extension (PTE) and Supplementary Protection Certificates (SPC) 50

2.4.2.3 Pediatric Investigations (EU) 52

2.4.3 Exclusivity Privileges Related to Regulatory Procedures 53

2.4.3.1 Data Exclusivity and Market Exclusivity 53

2.4.3.2 Orphan Drugs 54

2.5 Patent Lifecycle Management 57

2.5.1 Formulations and/or Galenics 57

2.5.2 Combination Products 57

2.5.3 Second or Higher Medical Indication 58

2.5.4 New Dosage Regimens 59

2.5.5 Further Options for Small Molecules 59

2.5.6 Divisional Applications 60

2.6 Conclusion 60

List of Abbreviations 60

References 61

Part II Drug Class Studies 65

3 Kinase Inhibitor Drugs 67

Peng Wu and Amit Choudhary

3.1 Introduction 67

3.2 Historical Overview 70

3.2.1 Before 1980 70

3.2.2 1980s 70

3.2.3 1990s 70

3.2.4 After 2000 72

3.3 Approved Kinase Inhibitors 72

3.3.1 FDA-Approved Non-Covalent Small-Molecule Kinase Inhibitors 74

3.3.1.1 Bcr–Abl Inhibitors 74

3.3.1.2 ErbB Family Inhibitors 77

3.3.1.3 VEGFR Family Inhibitors 77

3.3.1.4 JAK Family Inhibitors 78

3.3.1.5 ALK Inhibitors 78

3.3.1.6 MET Inhibitors 78

3.3.1.7 B-Raf Inhibitors 79

3.3.1.8 MEK Inhibitors 79

3.3.1.9 PI3K Inhibitor 79

3.3.1.10 CDK Inhibitor 80

3.3.2 FDA Approved Covalent Small Molecule Kinase Inhibitors 80

3.3.3 FDA-Approved Rapalogs 80

3.3.4 Other Approved Kinase Inhibitors 81

3.4 New Directions 82

3.5 Conclusion 83

List of Abbreviations 83

References 83

4 Evolution of Nonsteroidal Androgen Receptor Antagonists 95

Arwed Cleve and Duy Nguyen

4.1 Introduction 95

4.2 Flutamide (Eulexin®) 96

4.3 Nilutamide (Anandron®) 98

4.4 Bicalutamide (Casodex®) 99

4.5 Enzalutamide (Xtandi®) 102

4.6 Outlook 106

4.7 Conclusion 106

List of Abbreviations 106

References 107

Part III Case Studies 111