The synthesis and biological evaluation of 1-C-alkyl-L-arabinoiminofuranoses, a novel class of α-glucosidase inhibitors

Bioorg Med Chem Lett. 2011 Jan 15;21(2):738-41. doi: 10.1016/j.bmcl.2010.11.112. Epub 2010 Nov 30.

Abstract

The asymmetric synthesis of 1-C-alkyl-l-arabinoiminofuranoses 1 was achieved by asymmetric allylic alkylation (AAA), ring closing metathesis (RCM), and Negishi cross coupling as key reactions. Some of the prepared compounds showed potent inhibitory activities towards intestinal maltase, with IC(50) values comparable to those of commercial drugs such as acarbose, voglibose, and miglitol, which are used in the treatment of type 2 diabetes. Among them, the inhibitory activity (IC(50)=0.032μM) towards intestinal sucrase of 1c was quite strong compared to the above commercial drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / enzymology
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Glycoside Hydrolase Inhibitors*
  • Humans
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Imino Furanoses / chemical synthesis
  • Imino Furanoses / chemistry*
  • Imino Furanoses / pharmacology*
  • Rats
  • alpha-Glucosidases / metabolism*

Substances

  • Enzyme Inhibitors
  • Glycoside Hydrolase Inhibitors
  • Hypoglycemic Agents
  • Imino Furanoses
  • alpha-Glucosidases