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

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 compound 3b, 3d, 7d, 8d, and 9d showed a considerable anti‐lipase activity at various concentrations. The activity of compounds 7b (IC50 = 1.45 ± 0.12 μM) was the highest in terms of IC50, comparable to that of orlistat, a well‐known PL inhibitor used as an antiobesity drug.