[Iminosugars: current and future therapeutic applications]. 2007

O Martin
ICOA, Cnrs & Université d'Orléans, BP 6759, F 45067 Orléans Cedex. Olivier.Martin@univ-orelans.fr

The replacement of the oxygen-containing ring (pyranose, furanose) of monosaccharides by a nitrogen-containing ring (pyrrolidine, piperidine) leads to a particularly interesting class of glycomimetics: iminosugars. The first synthesis of such a sugar analog by Prof. H. Paulsen in 1966 (5-amino-5-deoxy-D-glucose) was followed by the discovery in Japan, a few months later, of the same compound from bacterial extracts by S. Inouye. The compound was named nojirimycin. Whereas this compound was shown in 1966 to exhibit modest antibiotic activities, the properties of iminosugars as powerful glycosidase inhibitors were discovered only many years later (1976) by chemists at Bayer. Since then, these compounds have been extensively studied and other biological properties have been discovered: inhibition of glycosyltransferases, of glycogen phosphorylase, of purine nucleoside phosphorylases, etc. The first therapeutic agent of this family is Miglitol, a drug that is used to modulate sugar absorption in the case of non-insulin-dependent diabetes; a second iminosugar has been recently put on the market, N-butyl-1-deoxynojirimycin, under the trade name Zavesca, for the treatment of lysosomal diseases (Gaucher disease in particular). Other therapeutic applications are under investigations, for example for the treatment of certain forms of cancer, of Fabry disease and viral infections (hepatitis B).

UI MeSH Term Description Entries
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D003276 Contraceptives, Oral Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both. Low-Dose Oral Contraceptive,Oral Contraceptive,Oral Contraceptives,Oral Contraceptives, Low-Dose,Oral Contraceptives, Phasic,Contraceptive, Low-Dose Oral,Contraceptive, Oral,Contraceptives, Low-Dose Oral,Contraceptives, Phasic Oral,Low Dose Oral Contraceptive,Low-Dose Oral Contraceptives,Oral Contraceptive, Low-Dose,Oral Contraceptives, Low Dose,Phasic Oral Contraceptives
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D016464 Lysosomal Storage Diseases Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates. Lysosomal Enzyme Disorders,Disease, Lysosomal Storage,Diseases, Lysosomal Storage,Disorder, Lysosomal Enzyme,Disorders, Lysosomal Enzyme,Enzyme Disorder, Lysosomal,Enzyme Disorders, Lysosomal,Lysosomal Enzyme Disorder,Lysosomal Storage Disease
D050111 Imino Sugars Sugars in which the OXYGEN is replaced by a NITROGEN atom. This substitution prevents normal METABOLISM resulting in inhibition of GLYCOSIDASES and GLYCOSYLTRANSFERASES. Sugars, Imino

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