Design and synthesis of N-(3,5-difluoro-4-hydroxyphenyl)benzenesulfonamides as aldose reductase inhibitors

Bioorg Med Chem. 2008 Apr 1;16(7):3926-32. doi: 10.1016/j.bmc.2008.01.042. Epub 2008 Jan 30.

Abstract

N-(3,5-Difluoro-4-hydroxyphenyl)benzenesulfonamide (4) and its derivatives 5-7 were prepared as putative bioisosteres of the previously reported aldose reductase inhibitors, which are the N-benzenesulfonylglycine derivatives I-IV. The in vitro aldose reductase inhibitory activity of the prepared compounds is higher than that of the respective glycine derivatives. Furthermore, the parent compound 4 reveals high antioxidant potential. Additionally, the intestine permeability of 4 is determined, and there is initial evidence that there is an operating influx mechanism. Overall, the data indicate that the presented chemotype could serve as a core structure for the design of putative pharmacotherapeutic agents, aiming to the long-term complications of diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Aldehyde Reductase / metabolism
  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Benzenesulfonamides
  • Biphenyl Compounds / metabolism
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Eye / drug effects
  • Eye / enzymology
  • Female
  • Fluorine Compounds / chemical synthesis*
  • Fluorine Compounds / chemistry
  • Fluorine Compounds / pharmacology*
  • Hydrazines / metabolism
  • Hydroxylation
  • Jejunum / drug effects
  • Lipid Peroxidation / drug effects
  • Male
  • Molecular Structure
  • Picrates
  • Rats
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Antioxidants
  • Biphenyl Compounds
  • Enzyme Inhibitors
  • Fluorine Compounds
  • Hydrazines
  • Picrates
  • Sulfonamides
  • 1,1-diphenyl-2-picrylhydrazyl
  • Aldehyde Reductase