Synthesis of new fluorine-containing 1,2,4-triazole-5-on derivatives with their anti-urease, anti-xanthine oxidase and antıoxidant activities

Abstract

Acetohydrazide derivatives (3a, b) were obtained starting from 3-(2 or 4-fluorobenzyl)-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-one (la, b) by two steps. Compounds 3a, b were converted to the corresponding methylideneacetohydrazide derivatives (4a-d). the treatment of compounds 3a, b with 4-fluorophenylisothiocyanate produced carbothioamide derivatives (5a, b). the cyclization of compounds 5a,b in the presence of NaOH resulted in the formation of compounds 6a, b. the reactions of compounds 6a, b with 4-fluorobenzyl bromide in the presence of sodium ethoxide afforded the corresponding S-(4-fluorobenzyl) derivatives (7a, b). on the other hand, the treatment of compounds 3a, b with CS2 in the presence of aqueous KOH afforded the 1,3,4-oxadiazole-5-thiones (8a, b) which were converted to N-Mannich bases 9a, b. the synthesized compounds 1-9 were screened for their urease and xanthine oxidase inhibition activities and antioxidant activity were evaluated. Especially, according to the CUPRAC and ABTS(center dot+) radical scavenging activity methods, 3a, 3b, 5a, 5b, 6a, 6b, 8a, 8b, 9a and 9b compounds showed strong antioxidant activity. Compound 4a exhibited good xanthine oxidase (XO) inhibition. Also, compounds 9b and 9a showed efficient urease inhibition at various concentrations.