Successful Drug Discovery, Volume 2

Janos Fischer , Wayne E. Childers 지음

Wiley-VCH 2016년 11월 04일 출간

작품소개

책소개

Retaining the successful approach found in the previous volume in this series, the inventors and primary developers of drugs that successfully made it to market tell the story of the drug's discovery and development and relate the often twisted route from the first candidate molecule to the final marketed drug. 11 selected case studies describe recently introduced drugs that have not been previously covered in textbooks or general references. These range across six different therapeutic fields and provide a representative cross-section of the current drug development efforts. Backed by copious data and chemical information, the insight and experience of the contributors makes this one of the most useful training manuals that a junior medicinal chemist can hope to find and has won the support and endorsement of IUPAC.

목차

Preface XIII List of Contributors XVII Part I HDAC Inhibitor Anticancer Drug Discovery 1 1 From DMSO to the Anticancer Compound SAHA, an Unusual Intellectual Pathway for Drug Design 3Ronald Breslow 1.1 Introduction 3 1.2 The Discovery of SAHA (vorinostat) 4 1.3 Clinical Trials 7 1.4 Follow-On Research Selective HDAC Inhibitors 8 1.5 Conclusion 9 References 9 2 Romidepsin and the Zinc-Binding Thiol Family of Natural Product HDAC Inhibitors 13A. Ganesan 2.1 Histone Deacetylases as a Therapeutic Target 13 2.2 The Discovery and Development of Romidepsin 15 2.3 The Zinc-BindingThiol Family of Natural Product HDAC Inhibitors 18 2.4 Synthetic Analogues of the Zinc-BindingThiol Natural Products 21 2.5 Summary 23 References 24 3 The Discovery and Development of Belinostat 31Paul W. Finn, Einars Loza and Elisabeth Carstensen 3.1 Introduction 31 3.2 Discovery of Belinostat 32 3.2.1 Design Strategy 32 3.2.2 Medicinal Chemistry and SAR 34 3.3 Belinostat Biological Profiling 41 3.3.1 Mode of Action and HDAC Isoform Selectivity 41 3.3.2 Antiproliferative and Antitumor Activity 42 3.4 Formulation Development 44 3.5 Clinical Development 45 3.5.1 Clinical Studies Leading to Approval and Other Clinical Investigations 45 3.5.2 Pharmacokinetics 49 3.5.3 Safety and Tolerability 51 3.6 Conclusions 52 References 53 4 Discovery and Development of Farydak (NVP-LBH589,Panobinostat) as an Anticancer Drug 59Peter Atadja and Lawrence Perez 4.1 Target Identification: From p21Waf1 Induction to HDAC Inhibition 59 4.2 Program Flowchart Assays for Drug Discovery 61 4.3 Hit-To-Lead Campaign: Trichostatin A to LAK974 63 4.4 Lead Optimization: LAK974 to LAQ824 64

작가정보

저자(글) Janos Fischer

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. 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. Wayne 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 Research, Inc., 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.

저자(글) Wayne E. Childers

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