Synthesis and pancreatic lipase inhibitory activities of some 1,2,4-triazol-5(3)-one derivatives

Abstract

In this study, starting from 4-amino-5-(4-chlorobenzyl)-2,4-dihydro-3H-1,2,4-triazole-3-one (1), the 4-Amino-5-(4-chlorobenzyl)-2-undecyl-2,4-dihydro-3H-1,2,4-triazol-3-one (2) was first synthesized and this compound was converted to Schiff base derivatives (3a-e). in the second step of the study, the 2-[3-(4-chlorobenzyl)-5-oxo-1-undecyl-1,5-dihydro-4H-1,2,4-triazole-4-yl]-acetohydrazide (6), which was used as a key product in the synthesis of many heterocyclic compounds was synthesized in four steps, and then this compound was converted into methylidene acetohydrazide (7a-e), thiosemicarbazide (8a-e), and 1,2,4-triazole-5-thione (9a-e) derivatives. Also, in the last part of the study, 1,2,4-triazole-5-thione derivatives were changed into Mannich bases (10a-b) bearing a 4-phenylpiperazine ring. These new compounds were tested with regard to pancreatic lipase (PL) inhibition activity, and compound3b,3d,7d,8d, and9dshowed a considerable anti-lipase activity at various concentrations. the activity of compounds7b(IC50= 1.45 +/- 0.12 mu M) was the highest in terms of IC50, comparable to that of orlistat, a well-known PL inhibitor used as an antiobesity drug.