Synthesis and biological evaluation of α-1-C-4'-arylbutyl-L-arabinoiminofuranoses, a new class of α-glucosidase inhibitors

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3298-301. doi: 10.1016/j.bmcl.2014.06.001. Epub 2014 Jun 11.

Abstract

A series of α-1-C-4'-arylbutyl-L-arabinoiminofuranoses 3 with functional groups attached to the phenyl ring, which are potential α-glycosidase inhibitors, was designed and synthesized by using a Negishi cross-coupling reaction as the key reaction. Arylbutyl derivatives 3a-e showed potent inhibitory activities against intestinal maltase. Among them, difluorophenylbutyl derivative 3e showed good inhibition activities against intestinal isomaltase and sucrase as compared to those of 1 and commercial drugs.

Keywords: 1-C-4′-Arylbutyl-l-arabinoiminofuranoses; Iminosugars; Structure–activity relationship; Type-2 diabetes; α-Glucosidase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Glycoside Hydrolase Inhibitors / chemical synthesis
  • Glycoside Hydrolase Inhibitors / chemistry
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Humans
  • Imino Sugars / chemical synthesis
  • Imino Sugars / chemistry
  • Imino Sugars / pharmacology*
  • Intestines / enzymology
  • Molecular Structure
  • Structure-Activity Relationship
  • alpha-Glucosidases / metabolism*

Substances

  • 1-(4-(3,5-difluorophenyl)butyl)iminofuranose
  • Glycoside Hydrolase Inhibitors
  • Imino Sugars
  • alpha-Glucosidases