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 compound 3b, 3d, 7d, 8d, and 9d showed a considerable anti-lipase activity at various concentrations. The activity of compounds 7b (IC 50 = 1.45 ± 0.12 μM) was the highest in terms of IC 50 , comparable to that of orlistat, a well-known PL inhibitor used as an antiobesity drug.

From Nitro- to Heterocycle-Functionalized 1,2,4-Triazol-3-one Derivatives: Achieving High-Performance Insensitive Energetic Compounds

“…The reactions are shown in Scheme 1. The structures of 2 and 5 were confirmed by 15 N NMR, single-crystal XRD, and other methods.…”

“…With the aid of two-dimensional (2D) 1 H− 15 N HMBC spectra and quantum calculations, all peaks from the 15 N spectra were assigned to the corresponding nitrogen atoms with high accuracy (Supporting Information). Their experimental and simulated 15 N NMR spectra are shown in Figure 3. In the 15 N NMR spectra, most nitrogen atoms in 1,2,4triazol-3-one appear upfield ranging from −333 to −172 (nitromethane as an external standard).…”

“…Their experimental and simulated 15 N NMR spectra are shown in Figure 3. In the 15 N NMR spectra, most nitrogen atoms in 1,2,4triazol-3-one appear upfield ranging from −333 to −172 (nitromethane as an external standard). Their chemical shifts do not show significant differences for either furazan or tetrazole substitution.…”

“…They are fully characterized by multinuclear NMR, IR, EA, and single-crystal XRD. The structures of the products are verified by 15 N NMR and single-crystal XRD. The reaction mechanism is also studied with quantum calculations.…”

“…Energetic materials represent a series of metastable chemicals that can store and release a vast amount of energy on demand. − Despite the fact that thousands of new potential explosives are designed and prepared every year, few can withstand the high standards and strict requirements to be not only highly energetic and insensitive but also environmentally friendly, thermally stable, cost-effective, and compatible with metal as well as other materials. − 5-Nitro-1,2,4-triazol-3-one (NTO), as a milestone in energetic material history, has superior properties with a high density, low sensitivity, and low cost. , Because NTO is a nitro-functionalized 1,2,4-triazol-3-one (TO) derivative, it is worth exploiting more energetic compounds based on the TO skeleton. However, a literature investigation indicates that TO derivatives are rarely reported as energetic materials (Figure a), − largely resulting from the lack of efficient methods for constructing the TO skeleton.…”