title: 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.
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 µg/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.
authors.affiliation: Faculty of Science, Department of Chemistry, Karadeniz Technical University, Trabzon, Turkey.
authors.forename: Olcay
authors.initials: O
authors.lastname: Bekircan
authors.forename: Emre
authors.initials: E
authors.lastname: Menteşe
authors.forename: Serdar
authors.initials: S
authors.lastname: Ulker
authors.forename: Cagatay
authors.initials: C
authors.lastname: Kucuk
mesh_terms: D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D000077403:Orlistat; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D004791:Enzyme Inhibitors; D007783:Lactones; D014230:Triazoles; C045575:1,2,4-triazole; D000077403:Orlistat; D008049:Lipase; D014510:Urease
keywords: 1,2,4-Triazoles; Anti-urease activities; Lipase inhibition; Mannich bases; Schiff bases