Fluorine in Medicinal Chemistry and Chemical Biology

The extraordinary potential of fluorine-containing molecules in medicinal chemistry and chemical biology has been recognized by researchers outside of the traditional fluorine chemistry field, and thus a new wave of fluorine chemistry is rapidly expanding its biomedical frontiers. With several of the best selling drugs in the world crucially containing fluorine atoms, the incorporation of fluorine to drug leads has become an essential practice in biomedical research, especially for drug design and discovery as well as development.

Focusing on the unique and significant roles that fluorine plays in medicinal chemistry and chemical biology, this book reviews recent advances and future prospects in this rapidly developing field. Topics covered include:

• Discovery and development of fluorine containing drugs and drug candidates.
• New and efficient synthetic methods for medicinal chemistry and the optimisation of fluorine-containing drug candidates.
• Structural and chemical biology of fluorinated amino acids and peptides.
• Fluorine labels as probes in metabolic study, protein engineering and clinical diagnosis.
• Applications of 19F NMR spectroscopy in biomedical research.

An appendix presents an invaluable index of all fluorine-containing drugs that have been approved by the US Food and Drug Administration, including information on structure and pharmaceutical action.

Fluorine in Medicinal Chemistry and Chemical Biology will serve as an excellent reference source for graduate students as well as academic and industrial researchers who want to take advantage of fluorine in biomedical research.

Introduction

Chapter 1 “Unique Properties of Fluorine and Their Relevance to Medicinal Chemistry and Chemical Biology” by Takashi Yamazaki, Takeo Taguchi and Iwao Ojima

Medicinal Chemistry

Chapter 2 “Fluorinated Prostanoids: Development of Tafluprost, a New Anti-glaucoma Agent” by Yasushi Matsumura

Chapter 3 “Fluorinated conformationally restricted glutamate analogs for CNS drug discovery and development” by Atsuro Nakazato

Chapter 4 “Fluorinated Inhibitors of Matrix Metalloproteinases” by Roberta Sinisi, Monika Jagodzinska, Gabriele Candiani, Florent Huguenot, Monica Sani, Alessandro Volonterio, Raffaella Maffezzoni and Matteo Zanda

Chapter 5 “Fluoro-Taxoid Anticancer Agents” by Antonella Pepe, Larisa Kuznetsova, Liang Sun and Iwao Ojima

Chapter 6 “Antimalarial Fluoroartemisinins: Increased Metabolic and Chemical Stability”by Jean-Pierre Bégué, Danièle Bonnet-Delpon

Chapter 7 “Synthesis and Biological Activity of Fluorinated Nucleosides” by Tokumi Maruyama, Masahiro Ikejiri, Kunisuke Izawa and Tomoyuki Onishi

Synthetic methods for medicinal chemistry and chemical biology

Chapter 8 “Synthesis of gem-Difluoromethylenated Nucleosides via gem-Difluoromethylene-Containing Building Blocks” by Wei-Dong Meng and Feng-Ling Qing

Chapter 9 “Recent Advances in the Syntheses of Fluorinated Amino Acids” by Kenji Uneyama

Chapter 10 “Fluorinated Moieties for Replacement of Amide and Peptide Bonds” by Takeo Taguchi and Hikaru Yanai

Chapter 11 “Perfluorinated Heteroaromatic Systems as Scaffolds for Drug Discovery” by David Armstrong, Matthew W. Cartwright, Emma L. Parks, Graham Pattison, Graham Sandford, Rachel Slater, John A. Christopher, David D. Miller, Paul W. Smith and Antonio Vong

Chapter 12 “gem-Difluorocyclopropanes as key building blocks for novel biologically active molecules” by Toshiyuki Itoh

Chapter 13 “Fluorous Mixture Synthesis (FMS) of Drug-Like Molecules and Enantiomers, Stereoisomers, and Analogs of Natural Products” by Wei Zhang

Chapter 14 “Fluorine-18 Radiopharmaceuticals” by Michael R. Kilbourn and Xia Shao

Applications of fluorinated amino acids and peptides to chemical biology and pharmacology

Chapter 15 “Application of Artificial Model Systems to Study the Interactions of Fluorinated Amino Acids within the Native Environment of Coiled Coil Proteins” by Mario Salwiczek, Toni Vagt and Beate Koksch

Chapter 16 “Fluorinated Amino Acids and Biomolecules in Protein Design and Chemical Biology” by He Meng, Ginevra A. Clark^, and Krishna Kumar

Chapter 17 “Effects of Fluorination on the Bioorganic Properties of Methionine” by John F. Honek

Chapter 18 “Structure analysis of membrane-active peptides using ¹⁹F-labeled amino acids and solid state NMR” by Parvesh Wadhwani and Erik Strandberg

Chapter 19 “Metabolism of Fluorine-containing Drugs using in vivo Magnetic Resonance Spectroscopy” by Erika Schneider

Appendix

“FDA-Approved Active Pharmaceutical Ingredients Containing Fluorine” by Elizabeth Pollina-Cormier, Manisha Das, and Iwao Ojima Professor Iwao Ojima is Distinguished Professor in the Department of Chemistry, and Director of the Institute of Chemical Biology & Drug Discovery, at the State University of New York at Stony Brook. He has published over 340 papers and reviews, more than 140 patents and patent applications, and edited 5 books, including Biomedical Frontiers of Fluorine Chemistry, published in the ACS Symposium Series in 1996. The extraordinary potential of fluorine-containing biologically relevant molecules in biology, medicinal chemistry, and medical applications has been recognized by researchers who are not in the traditional fluorine chemistry field, and thus a new wave of fluorine chemistry is expanding its biomedical frontiers. This book contains comprehensive reviews on cutting-edge developments and future prospects of fluorine in bioorganic and medicinal chemistry. It is essential for researchers who want to take advantage of the use of fluorine in biomedical research, from rational drug design, theory and synthesis to the use of fluorine labels as probes in metabolic study, protein engineering, and clinical diagnosis.