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-akind 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.

Arun K. Ghosh studied chemistry at the University of Calcutta and the Indian Institute of Technology, Kanpur (India). He obtained his Ph.D. at the University of Pittsburgh (USA) and pursued postdoctoral research at Harvard University. 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: National Institutes of Health MERIT Award, IUPAC Richter Award, Arthur C. Cope Scholar Award, Robert Scarborough Medicinal Chemistry Award. He has published over 225 research papers and holds numerous patents. Professor Ghosh's research interests include diverse areas of organic, bioorganic, and medicinal chemistry with particular emphasis on organic synthesis and structure-based design of biomolecules.
Sandra Gemma received her Laurea in Pharmacy at the University of Siena (Italy), followed by a PhD in Medicinal Chemistry at the same University. In 2004 she was post-doctoral fellow at the Department of Chemistry of the University of Illinois at Chicago (USA). Since 2006 she is a permanent researcher at the University of Siena, Faculty of Pharmacy. Dr. Gemma?s scientific activity is documented by 47 journal publications. Her research has focused on the synthesis of ligands for GPCRs and ion channels, and on the structure- and ligand-based development of antiviral and antimalarial compounds.

PRINCIPLES, TOOLS, AND TECHNIQUES FOR STRUCTURE-BASED DRUG DESIGN
The evolution of structure-based drug discovery
Molecular interactions and thermodynamics of receptor-ligand complexes
Enzyme inhibition
Drug-like compounds and privileged structures
Isosterism and bioisosterism as tools for ligand design and optimization in the context of structure-based design
Protein X-ray crystallography: from the structure of hemoglobin to high-throughput crystallography and its application to fragment-based drug discovery
NMR: an important technique for the structure elucidation of proteins and for ligand design

LIGAND AND SCAFFOLD SYNTHESIS FOR STRUCTURE-BASED DESIGN
Preparation of functionalized building blocks for structure-based drug design
Robust synthetic methodologies for structural decoration

MOLECULES THAT HAVE BECOME MEDICINES
Zinc an aspartic acid protease inhibitors as antihypertensive agents
Carbonic anhydrase inhibitors
Antivirals
Protease inhibitors as anticoagulants
Anticancer agents
Structure-based design for GPCRs