Synthesis of Some New 1,2,4-Triazole Derivatives Starting from 3-(4-Chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol with Anti-Lipase and Anti-Urease Activities


BEKİRCAN O., Menteşe E., Ülker S., Küçük C.

ARCHIV DER PHARMAZIE, vol.347, no.6, pp.387-397, 2014 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 347 Issue: 6
  • Publication Date: 2014
  • Doi Number: 10.1002/ardp.201300344
  • Journal Name: ARCHIV DER PHARMAZIE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.387-397
  • Keywords: Anti-urease activities, Lipase inhibition, Mannich bases, Schiff bases, 1,2,4-Triazoles, TRIAZOLE ANTIFUNGAL, INHIBITORS, ENZYMES
  • Karadeniz Technical University Affiliated: Yes

Abstract

In the present study, starting compound 4 was prepared by deamination of compound 2 in the presence of hypophosphorous acid and sodium nitrite. Treatment of compound 4 with ethyl bromoacetate produced ethyl[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetate (5), which was converted to the hydrazide derivative (6) by treatment with hydrazine hydrate. The reaction of compound 6 with aromatic aldehydes resulted in the formation of arylidene hydrazides (7). Treatment of 6 with CS2 in the presence of potassium hydroxide (KOH), followed by cyclization with hydrazine hydrate, afforded 4-amino-5-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione (9). The condensation of 9 with appropriate aldehydes gave Schiff bases (10), which were converted into Mannich bases (11) in the presence of formaldehyde. All the synthesized compounds were screened for their anti-lipase and anti-urease activities. Compounds 7b, 7d, 11b, 11c, and 11d showed moderate-to-good lipase inhibitory effects compared to orlistat. Compounds 7b and 7d exhibited better anti-lipase activity. Furthermore, among the compounds tested, 11a and 11d were found to show high inhibitory effect against urease with IC50 values of 12.39 +/- 0.35 and 16.12 +/- 1.06 mu g/mL, respectively. Compound 11c showed moderate inhibitory activity. The Mannich base containing compound 11 may be a source of good leads for the synthesis of lipase and urease dual inhibitors.