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.
Shadia A Galal  1 ,  Muhammad Khattab  2 ,  Fotini Andreadaki  3 ,  Evangelia D Chrysina  4 ,  Jean-Pierre Praly  5 ,  Fatma A F Ragab  6 ,  Hoda I El Diwani  2
Affiliations
  • 1. Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622 Cairo, Egypt. Electronic address: [email protected].
  • 2. Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622 Cairo, Egypt.
  • 3. Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, Athens GR-11635, Greece.
  • 4. Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, Athens GR-11635, Greece. Electronic address: [email protected].
  • 5. Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique 2-Glycochimie, UMR 5246, CNRS, Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, F-69622 Villeurbanne, France. Electronic address: [email protected].
  • 6. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
PMID: 27624527 DOI: 10.1016/j.bmc.2016.08.069
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.