Gem-diamine 1-N-iminosugars as versatile glycomimetics: synthesis, biological activity and therapeutic potential.
Iminosugars, which carry a basic nitrogen in the carbohydrate ring, have attracted increasing interest as new glycomimetics. Gem-diamine 1-N-iminosugars, a new class of iminosugars, have a nitrogen atom in place of the anomeric carbon. Various kinds of 1-N-iminosugars have been synthesized from glyconolactones as a chiral source in a totally stereospecific manner and/or by the convergent strategy from siastatin B, a secondary metabolite of Streptomyces. The protonated form of 1-N-iminosugar mimics the charge at the anomeric position in the transition state of enzymatic glycosidic hydrolysis, resulting in a strong and specific inhibition of glycosidases and glycosyltransferases. They have been recently recognized as a new source of therapeutic drug candidates in a wide range of diseases associated with the carbohydrate metabolism of glycoconjugates, such as tumor metastasis, influenza virus infection, lysosomal storage disorder and so forth.
Nishimura
Yoshio
Y
Bioactive Molecules Research Group, Microbial Chemistry Research Center, Shinagawa-ku, Tokyo, Japan. nishimuray@bikaken.or.jp
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005690:Galactose / Q000138:chemical synthesis / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D050112:Imino Pyranoses / Q000138:chemical synthesis / Q000494:pharmacology; D007202:Indicators and Reagents; D007251:Influenza, Human / Q000188:drug therapy; D016464:Lysosomal Storage Diseases / Q000188:drug therapy; D051379:Mice; D009362:Neoplasm Metastasis / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D050112:Imino Pyranoses; D007202:Indicators and Reagents; C119511:galactose-type gem-diamine 1-N-iminosugar; D005947:Glucose; D005690:Galactose