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Synthesis of Some New 1,2,4‐Triazole Derivatives Starting from 3‐(4‐Chlorophenyl)‐5‐(4‐methoxybenzyl)‐4 H ‐1,2,4‐triazol with Anti‐Lipase and Anti‐Urease Activities
Author(s) -
Bekircan Olcay,
Menteşe Emre,
Ülker Serdar,
Kucuk Cagatay
Publication year - 2014
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201300344
Subject(s) - chemistry , ethyl bromoacetate , lipase , hydrazine (antidepressant) , hydrazide , mannich base , hydrate , organic chemistry , ethyl acetoacetate , urease , 1,2,4 triazole , sodium nitrite , medicinal chemistry , enzyme , catalysis , chromatography
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)‐4 H ‐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 CS 2 in the presence of potassium hydroxide (KOH), followed by cyclization with hydrazine hydrate, afforded 4‐amino‐5‐{[3‐(4‐chlorophenyl)‐5‐(4‐methoxybenzyl)‐4 H ‐1,2,4‐triazol‐4‐yl]methyl}‐2,4‐dihydro‐3 H ‐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 IC 50 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.