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Summary

Iminosugars form undoubtedly the most attractive of carbohydrate mimics reported so far. In these structures, the substitution of the endocyclic oxygen of sugars by a basic nitrogen atom leads to remarkable biological properties and raises many challenges in organic synthesis. Since the discovery of their biological activity as glycosidase inhibitors in the 1970's, these polyvalent molecules have progressively made their way from the laboratory to the clinic.The impressive series of discoveries in the field over the past ten years indicates clearly that it is "a boom time" for iminosugar chemistry and biology. The scope of their profile as inhibitors has been extended to a number of enzymes such as phosphorylases, glycosyltransferases or metalloproteinases, and iminosugars now constitute lead compounds for the development of new therapeutic agents for a wide range of diseases including diabetes, viral infections, lysosomal storage disorders and tumor metastasis.Latest developments, from iminosugar synthesis to their use in clinical studies, are presented in this book, which contains contributions from over fifteen of the major chemists, biochemists and drug developers in this rapidly expanding field. An extensive table correlating the structures of more than 600 iminosugars of therapeutic interest with their biological activities is also included in the book and should prove particularly useful to aid with the design and the discovery of novel bioactive substances.Iminosugars: From Synthesis to Therapeutic Application provides a unique resource for academic and industrial researchers working in the field of iminosugars and glycomimetics of biological and/or therapeutic interest: organic chemists, medicinal chemists, carbohydrate chemists and medical scientists.

Table of Contents

Foreward
Preface
List of Contributors
Iminosugars: past, present and future
Naturally occurring iminosugars and related alkaloids: structure, activity and applications
Introduction
?-Glucosidase inhibitors
ß-Glucosidase inhibitors
?- and b-Galactosidase inhibitors
?-Mannosidase inhibitors
Concluding remarks and future prospects
References
General strategies for the synthesis of iminosugars and new approaches towards iminosugar libraries
Introduction
Monocyclic compounds
1-N-Iminosugars
Bicyclic compounds
Other bicyclic compounds
Iminosugar conjugates
Conclusions
References
Iminosugar C-glycosides: synthesis and biological activity
Introduction
Synthesis of iminosugar C-glycosides
Biological activity of iminosugar C-glycosides
Conclusion
References
Imino-C-disaccharides and analogues: synthesis and biological activity
Introduction
Synthesis of imino-C-disaccharides
Conformations of imino-C-disaccharides
Glycosidase inhibitory activities of imino-C-disaccharides
Efficient combinatorial method for the discovery of glycosidase inhibitors
Antitumour activity of new a-mannosidase inhibitors
Conclusion
References
Isofagomine, noeuromycin and other 1-azasugars, iminosugar related glycosidase inhibitors
Introduction
1-Azasugars that are piperidines (isofagomine, noeuromycin, etc.
1-Azasugars that are hydrazines
1-Azasugars that are oxazines
1-Azasugars that are piperidones
Sulphur-containing analogues of 1-azasugars
Slow inhibition and thermodynamics of binding
Are 1-azasugars (and iminosugars) transition state analogues?
References
Iminosugar-based glycosyltransferase inhibitors
Biological role and structural features of glycosyltransferases
Development of inhibitors of glycosyltransferases
Conclusion
References
Transition state analogue inhibitors of N-Ribosyltransferases
Introduction
Nucleoside hydrolases
Purine nucleoside phosphorylases (PNPs
5'-Methylthioadenosine (MTA) nucleosidases and phosphorylases
Ricin A-chain
Summary and conclusions
References
Iminosugars as antiviral agents
Introduction
The relationship between glucosidase inhibition and antiviral action
Fate of viral glycoproteins in glucosidase-inhibited cells
Specificity of glucosidase inhibition
N-Alkyl DNJs inhibit virus growth by non-glucosidase inhibitory mechanisms - other potential activities of these compounds
New directions for improving glucosidase inhibitors as antiviral agents
References
Iminosugars as active-site-specific chaperones for the treatment of lysosomal storage disorders
Introduction
Degradation of glycosphingolipids
Lysosomal enzyme biosynthesis and ER-associated degradation (ERAD
Active-site-specific chaperones and iminosugars
Basic requirements for effective ASSCs
Identification of ASSCs
Examples of ASSC therapy for lysosomal storage disorders
Future perspectives
References
Iminosugar inhibitors for substrate reduction therapy for the lysosomal glycosphingolipidoses
Glycolipid lysosomal storage diseases
Options for glycosphingolipidosis therapy
Iminosugars for substrate reduction therapy
Iminosugars as inhibitors of glycolipid biosynthesis
SRT combination therapy
Prospects for iminosugars as therapeutics
References
Iminosugar-based antitumoural agents
Introduction
Hexose-mimetic iminosugars
Hexuronic acid-mimetic iminosugars
Concluding remarks
References
Medicinal use of iminosugars
Introduction
Recent pharmaceutical developments
Clinical application of iminosugars as medicines
Conclusions
References
Tables of iminosugars, their biological activities and their potential as therapeutic agents
Introduction
Type 2 diabetes
Antiviral activities
Antibacterial activities
Antiprotozoal activities
Antiparasitarial activities
Cancer
Lysosomal diseases
Immunomodulating agents
Antipsoriatic agents
Antifungal agents
Cystic fibrosis
Infertility inducing agents
Chondroprotective agents
Inflammatory diseases
Appetite suppressing agents
Nematicidal activity
Insecticidal activity
References
Index
Table of Contents provided by Publisher. All Rights Reserved.

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