Synthesis of (benzimidazol-2-yl)aniline derivatives as glycogen phosphorylase inhibitors

Bioorg Med Chem. 2016 Nov 1;24(21):5423-5430. doi: 10.1016/j.bmc.2016.08.069. Epub 2016 Sep 1.

Abstract

A series of (benzimidazol-2-yl)-aniline (1) derivatives has been synthesized and evaluated as glycogen phosphorylase (GP) inhibitors. Kinetics studies revealed that compounds displaying a lateral heterocyclic residue with several heteroatoms (series 3 and 5) exhibited modest inhibitory properties with IC50 values in the 400-600μM range. Arylsulfonyl derivatives 7 (Ar: phenyl) and 9 (Ar: o-nitrophenyl) of 1 exhibited the highest activity (series 2) among the studied compounds (IC50 324μM and 357μM, respectively) with stronger effect than the p-tolyl analogue 8.

Keywords: Benzimidazole; Enzyme inhibition; Glycogen phosphorylase; Heterocycles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemical synthesis
  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology*
  • Animals
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glycogen Phosphorylase / antagonists & inhibitors*
  • Glycogen Phosphorylase / metabolism
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Rabbits
  • Structure-Activity Relationship

Substances

  • Aniline Compounds
  • Benzimidazoles
  • Enzyme Inhibitors
  • Glycogen Phosphorylase