Condensed bridgehead nitrogen heterocyclic system: synthesis and pharmacological activities of 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole derivatives of ibuprofen and biphenyl-4-yloxy acetic acid

Eur J Med Chem. 2008 Oct;43(10):2056-66. doi: 10.1016/j.ejmech.2007.09.025. Epub 2007 Oct 6.

Abstract

Several 3,6-disubstituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazoles were prepared by condensation of 4-amino-5-substituted-3-mercapto-(4H)-1,2,4-triazoles (3a,b) with various substituted aromatic acids and aryl/alkyl isothiocyanates through a one-pot reaction. These compounds were investigated for their anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, antibacterial and antifungal activities. Some of the synthesized compounds showed potent anti-inflammatory activity along with minimal ulcerogenic effect and lipid peroxidation, compared to those of ibuprofen and flurbiprofen. Some of the tested compounds also showed moderate antimicrobial activity against tested bacterial and fungal strains.

MeSH terms

  • Acute Disease
  • Analgesics / chemistry
  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Analgesics / toxicity
  • Animals
  • Bacteria / drug effects
  • Diphenylacetic Acids / chemistry*
  • Diphenylacetic Acids / pharmacology*
  • Diphenylacetic Acids / therapeutic use
  • Diphenylacetic Acids / toxicity
  • Female
  • Fungi / drug effects
  • Hepatocytes / drug effects
  • Ibuprofen / analogs & derivatives*
  • Ibuprofen / pharmacology*
  • Ibuprofen / therapeutic use
  • Ibuprofen / toxicity
  • Inflammation / drug therapy
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Rats
  • Thiadiazoles / chemistry*
  • Triazoles / chemistry*
  • Ulcer / etiology

Substances

  • Analgesics
  • Diphenylacetic Acids
  • Thiadiazoles
  • Triazoles
  • 1,2,4-triazole
  • diphenylacetic acid
  • Ibuprofen