Synthesis, biological evaluation and docking analysis of a new series of methylsulfonyl and sulfamoyl acetamides and ethyl acetates as potent COX-2 inhibitors

Bioorg Med Chem. 2015 Feb 15;23(4):810-20. doi: 10.1016/j.bmc.2014.12.041. Epub 2014 Dec 26.

Abstract

We report herein the synthesis, biological evaluation and docking analysis of a new series of methylsulfonyl, sulfamoyl acetamides and ethyl acetates that selectively inhibit cyclooxygenase-2 (COX-2) isoform. Among the newly synthesized compounds, some of them were endowed with a good activity against COX-2 and a good selectivity COX-2/COX-1 in vitro as well as a desirable analgesic activity in vivo, proving that replacement of the ester moiety with an amide group gave access to more stable derivatives, characterized by a good COX-inhibition.

Keywords: Analgesic agents; Anti-inflammatory agents; COX-2 inhibitors; Diarylpyrroles; Medicinal chemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemical synthesis
  • Acetamides / chemistry*
  • Acetamides / pharmacology*
  • Acetates / chemical synthesis
  • Acetates / chemistry*
  • Acetates / pharmacology*
  • Analgesics / chemical synthesis
  • Analgesics / chemistry
  • Analgesics / pharmacology
  • Animals
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / chemistry*
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Drug Design
  • Humans
  • Methylation
  • Mice
  • Molecular Docking Simulation
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Structure-Activity Relationship
  • Sulfur Compounds / chemical synthesis
  • Sulfur Compounds / chemistry
  • Sulfur Compounds / pharmacology

Substances

  • Acetamides
  • Acetates
  • Analgesics
  • Cyclooxygenase 2 Inhibitors
  • Sulfur Compounds
  • ethyl acetate
  • Cyclooxygenase 1
  • Cyclooxygenase 2