Bioorganic and Medicinal Chemistry of Fluorine
1. Auflage Juni 2008
384 Seiten, Hardcover
Wiley & Sons Ltd
Kurzbeschreibung
This book thoroughly overviews the role of fluorine in pharmaceutical science and development, including the classification of marketed and in-development fluorinated pharmaceuticals. The first part introduces the preparation of fluorinated compounds and their specific properties. The second part deals with fluorinated analogues of natural products, fluorinated amino acids and peptides, and derivatives of sugars. This section also includes a detailed chapter about the conception of enzyme inhibitors. In the final part, the main fluorinated pharmaceuticals, marketed or in development, are classified according to their therapeutic classes.
The diverse applications of fluorine in bioorganic and medicinal chemistry
The discovery of fluorouracil, fluorocorticoids, and fluoroquinolones has led to expanded interest in and usage of fluorine in chemistry. The first comprehensive reference dedicated to detailing the influence of fluorine on the structural properties of a molecule and on a molecule's biological behavior, Bioorganic and Medicinal Chemistry of Fluorine uses examples of fluorinated drugs to provide a thorough overview of the role of fluorine in pharmaceutical science and development. Covering established drugs as well as innovative and promising ideas, it includes:
* An introduction to the structural, physical, and chemical properties of fluorinated compounds and their preparations
* An examination of fluorinated analogues of natural products, fluorinated amino acids and peptides, and saccharidic derivatives
* A discussion of the inhibition of enzymes by fluorinated compounds
* An overview of existing fluorinated pharmaceuticals as well as some in development, categorized according to their therapeutic classes
Complete with references for further study, this is the premier resource on fluorine for pharmaceutical and medicinal chemists in academia and industry, researchers in organic chemistry and biochemistry, and advanced students and educators in pharmaceutical and medicinal chemistry, biochemistry, and organic chemistry.
Preface to the English Edition
1 General Remarks on Structural, Physical, and Chemical Properties of Fluorinated Compounds.
1.1 Structural Effects.
1.2 Physical Properties.
1.3 Effects on Electronic Properties and Reactivity.
References.
2 Overview on the Preparation of Fluorinated Compounds.
2.1 Preparation of Monofluorinated Compounds.
2.2 Preparation of Difluorinated Compounds.
2.3 Preparation of Trifluoromethyl Compounds.
2.4 Synthesis of Perfluoroalkyl Compounds.
References.
3 Effects of Fluorine Substitution on Biological Properties.
3.1 Affinity for the Macromolecule Target.
3.2 Absorption.
3.3 Metabolism.
3.4 Modification of Chemical Reactivity: Enzyme Inhibitors.
References.
4 Fluorinated Analogues of Natural Products.
4.1 Fluorinated Products in Nature.
4.2 Steroids.
4.3 Terpenes.
4.4 Pigments and Vitamins.
4.5 Lipids and Prostanoids.
4.6 Pheromones and Toxins.
4.7 Alkaloids.
4.8 Macrolides.
4.9 Anthracyclines.
References.
5 Fluorinated Derivatives of a-Amino Acids and Proteins.
5.1 Fluorinated Aliphatic Amino Acids.
5.2 Aromatic Amino Acids: Phenylalanine, Tyrosine, Histidine, and Tryptophan.
5.3 Functional Fluorinated Amino Acids.
5.4 -Fluoroalkyl Amino Acids.
5.5 Incorporation of Fluorinated Amino Acids into Peptides and Proteins.
References.
6 Saccharidic Fluorinated Derivatives.
6.1 Glycosyl Fluorides.
6.2 Mono- and Difluorinated Analogues of Sugars.
6.3 Fluoromethyl Derivatives of Sugars.
6.4 Perfluoroalkylated Sugars.
References.
7 Inhibition of Enzymes by Fluorinated Compounds.
7.1 Substrate Analogues.
7.2 Destabilization of Reaction Intermediates (or of Transition States) of Enzymatic Processes by Fluorinated Groups.
7.3 Inhibitors that are Analogues of the Transition State: Di- and Trifluoromethyl Ketones.
7.4 Mechanism-Based Inhibitors.
4,6-Dehydratase (CDP D-Glucose 4,6-Dehydratase).
7.5 Fluorinated Inhibitors Involving a Still Unknown Mechanism.
References.
8 Fluorinated Drugs.
8.1 Antitumor and Antiviral Fluorinated Drugs.
8.2 Anti-infectious Drugs.
8.3 Drugs for CNS Disorders.
8.4 Drugs of Inflammatory and Immunity Disorders.
8.5 Drugs for Cardiovascular Disorders.
8.6 Drugs for Gastrointestinal Disorders.
8.7 Drugs for Endocrine and Metabolic Disorders.
8.8 Miscellaneous.
8.9 Highly Fluorinated Compounds with Clinical Uses.
8.10 Fluorinated Functions and Motifs in Medicinal Chemistry.
Appendix: INN and Trademark Names.
References.
Index.
