Synthesis of 3,6-disubstituted 7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines as novel analgesic/anti-inflammatory compounds

AYTAÇ S. A., Tozkoparan B., KAYNAK F. B., Aktay G., Goektas O., Uenuevar S.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol.44, no.11, pp.4528-4538, 2009 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 44 Issue: 11
  • Publication Date: 2009
  • Doi Number: 10.1016/j.ejmech.2009.06.026
  • Journal Name: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.4528-4538
  • Keywords: Aminomercaptotriazoles, Triazolothiadiazines, Analgesic/anti-inflammatory activity, Antioxidant activity, DERIVATIVES, IBUPROFEN
  • Hacettepe University Affiliated: Yes

Abstract

In this study, a new class of 4-amino-3-substituted-1,2,4-triazole-5-thiones (1-4) and their corresponding condensed derivatives 3,6-disubstituted 7H-1,2,4-triazolo[3,4-bi-1,3,4-thiadiazines (1a-4c) were synthesized and evaluated for their analgesic/anti-inflammatory activities. All synthesized compounds were also tested for their gastric toxicity and antioxidant activity on acute administration. Most of the compounds showed significant activity in both carrageenan-induced oedema and acetic acid-induced writhing tests besides negligible gastrointestinal toxicity. The compounds showing less ulcerogenic effect also showed less lipid peroxidation (LPO) level. Most promising results were obtained with the compounds that placed a fluoro or a chloride on the phenyl ring at the sixth position of the fused ring. (C) 2009 Elsevier Masson SAS. All rights reserved.