SUCCESSFUL DRUG DISCOVERY, VOLUME 2

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 3
2 Romidepsin and the Zinc-Binding Thiol Family of Natural Product HDAC Inhibitors 13
3 The Discovery and Development of Belinostat 31
4 Discovery and Development of Farydak (NVP-LBH589,Panobinostat) as an Anticancer Drug 59
5 Discovery and Development of HDAC Subtype Selective Inhibitor Chidamide: Potential Immunomodulatory Activity Against Cancers 89
• Part II Steroidal CYP17 Inhibitor Anticancer Drug Discovery 115
6 Abiraterone Acetate (Zytiga): AnInhibitor of CYP17 as a Therapeutic for Castration-Resistant Prostate Cancer 117
• Part III Anti-Infective Drug Discoveries 137
7 Discovery of Delamanid for the Treatment of Multidrug-Resistant Pulmonary Tuberculosis 139
8 Sofosbuvir: The Discovery of a Curative Therapy for the Treatment of Hepatitis C Virus 163
• Part IV Central Nervous System (CNS) Drug Discovery 189
9 The Discovery of the Antidepressant Vortioxetine and the Research that Uncovered Its Potential to Treat the Cognitive Dysfunction Associated with Depression 191
• Part V Antiulcer Drug Discovery 215
10 Discovery of Vonoprazan Fumarate (TAK-438) as a Novel, Potent and Long-Lasting Potassium-Competitive Acid Blocker 217
• Part VI Cross-Therapeutic Drug Discovery (Respiratory Diseases/Anticancer) 235
11 Discovery and Development of Nintedanib: A Novel Antiangiogenic and Antifibrotic Agent 237
References 258
Index 267

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.

Author Information
• 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.
• 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.