1. Edition - June 2008
92.90 Euro
2008. 366 Pages, Hardcover
ISBN-10: 0-470-27830-7
ISBN-13: 978-0-470-27830-7 - John Wiley & Sons









Short description
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.

From the contents
Foreword.

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.