Structure–based Design of Drugs and Other Bioactive Molecules: Tools and Strategies

Drug design is a complex, challenging and innovative research area. Structure–based molecular design has transformed the drug discovery approach in modern medicine. Traditionally, focus has been placed on computational, structural or synthetic methods only in isolation. This one–of–a kind guide integrates all three skill sets for a complete picture of contemporary structure–based design. This practical approach provides the tools to develop a high–affinity ligand with drug–like properties for a given drug target for which a high–resolution structure exists. The authors use numerous examples of recently developed drugs to present ?best practice? methods in structurebased drug design with both newcomers and practicing researchers in mind. By way of a carefully balanced mix of theoretical background and case studies from medicinal chemistry applications, readers will quickly and efficiently master the basic skills of successful drug design. This book is aimed at new and active medicinal chemists, biochemists, pharmacologists, natural product chemists and those working in drug discovery in the pharmaceutical industry. It is highly recommended as a desk reference to guide students in medicinal and chemical sciences as well as to aid researchers engaged in drug design today.

From Traditional Medicine to Modern Drugs: Historical Perspective of Structure–Based Drug Design CONCEPTS, TOOLS, LIGANDS AND SCAFFOLDS FOR STRUCTURE–BASED DESIGN OF INHIBITORS Design of Inhibitors of Aspartic Acid Proteases Design of Serine Protease Inhibitors Design of Proteosome Inhibitors Design of Cysteine Protease Inhibitors Design of Metalloprotease Inhibitors Structure–Based Design of Protein Kinase Inhibitors Protein X–Ray Crystallography in Structure–Based Drug Design Structure–Based Design Strategies for Targeting G–Protein Coupled Receptors (GPCRs) STRUCTURE–BASED DESIGN OF FDA APPROVED INHIBITOR DRUG AND DRUGS UNDERGOING CLINICAL DEVELOPMENT Angiotensin–Converting Enzyme Inhibitors for the Treatment of Hypertension: Design and Discovery of Captopril HIV–1 Protease Inhibitors for the Treatment of HIV Infection and AIDS: Design of Saquinavir, and Darunavir Protein Kinase Inhibitor Drugs for Targeted Cancer Therapy: Design and Discovery of Imatinib, Nilotinib and Dasatinib NS3/4A Serine Protease Inhibitors for the Treatment of HCV: Design and Discovery of Boceprevir and Telaprevir Proteasome Inhibitors for the Treatment of Relapsed Multiple Myeloma: Design and Discovery of Bortezomib and Carfilzomib Direct Thrombin Inhibitors as Anticoagulant Drugs Non–Nucleoside HIV Reverse Transcriptase Inhibitors for the Treatment of HIV/AIDS: Design and Development of Etravirine Discovery of Aliskiren: First in Class Inhibitor of Renin Structure–Based Discovery of Neuraminidase Inhibitors against Influenza Virus Pandemics Threaten Carbonic Anhydrase Inhibitors for the Treatment of Glaucoma Beta–Secretase Inhibitors for the Treatment of Alzheimer′s Disease: Preclinical and Clinical Inhibitors

Arun K. Ghosh received his BS and MS in Chemistry at the University of Calcutta and the Indian Institute of Technology, Kanpur, respectively. He obtained his Ph.D. (1985) at the University of Pittsburgh. He then pursued post–doctoral research with Professor E. J. Corey at Harvard University (1985?1988). He was a research fellow at Merck Research Laboratories prior to joining the University of Illinois, Chicago as an assistant Professor in 1994. In 2005, he moved to Purdue University where he is currently the Ian P. Rothwell Distinguished Professor of Chemistry and Medicinal Chemistry. His notable honors include: ACS Medicinal Chemistry Hall of Fame, National Institutes of Health MERIT Award, CRSI medal from the Chemical Research Society of India, IUPAC Richter Award, ACS Arthur C. Cope Scholar Award, ACS Robert Scarborough Medicinal Chemistry Award, American Association for the Advancement of Science, University of Illinois University Scholar, National Merit Scholar of India. He has published over 260 research papers, edited a book on aspartic acid proteases and holds numerous patents. His research interests include diverse areas of organic, bioorganic, and medicinal chemistry with particular emphasis on organic synthesis and protein–structure–based design of biomolecules. Sandra Gemma graduated cum Laude in Medicinal Chemistry at the School of Pharmacy of the University of Siena (1998) where she also received her Ph.D. degree (2003). She was a post–doctoral fellow at the Department of Chemistry of the University of Illinois at Chicago in Professor Ghosh?s laboratory (2004 to 2005). She then moved back to the University of Siena where she was appointed as an Assistant Professor at the Department of Biotechnology, Chemistry and Pharmacy (2006?present). She also visited the Department of Chemistry at Purdue University as a research assistant in the Ghosh group (2008 and 2012). In 2014, Dr. Gemma received the National scientific qualification for the role of Associate Professor. Her research activity is currently focused on the structure– and ligand–based design of therapeutic agents, anti–HIV and anti–Alzheimer therapeutics, ligands for GPCRs and ion channels, and antimalarial drugs. She has authored more than 65 papers and patents in these fields.