Novel 5-substituted 1H-tetrazoles as cyclooxygenase-2 (COX-2) inhibitors

Bioorg Med Chem Lett. 2012 Mar 15;22(6):2235-8. doi: 10.1016/j.bmcl.2012.01.093. Epub 2012 Feb 2.

Abstract

A series of novel 5-substituted 1H-tetrazoles as cyclooxygenase-2 (COX-2) inhibitors was prepared via treatment of various diaryl amides with tetrachlorosilane/sodium azide. All compounds were tested in cyclooxygenase (COX) assays in vitro to determine COX-1 and COX-2 inhibitory potency and selectivity. Tetrazoles contained a methylsulfonyl or sulfonamide group as COX-2 pharmacophore displayed only low inhibitory potency towards COX-2. Most potent compounds showed IC(50) values of 6 and 7 μM for COX-2. All compounds showed IC(50) values greater 100 μM for COX-1 inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Biological Assay
  • Celecoxib
  • Chlorides / chemistry
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / chemical synthesis*
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Drug Design
  • Humans
  • Models, Molecular
  • Pyrazoles / pharmacology
  • Silicon Compounds / chemistry
  • Sodium Azide / chemistry
  • Structure-Activity Relationship
  • Sulfonamides / pharmacology
  • Tetrazoles / chemical synthesis*
  • Tetrazoles / pharmacology

Substances

  • Amides
  • Chlorides
  • Cyclooxygenase 2 Inhibitors
  • Pyrazoles
  • Silicon Compounds
  • Sulfonamides
  • Tetrazoles
  • Sodium Azide
  • silicon tetrachloride
  • Cyclooxygenase 2
  • Celecoxib