In vivo metabolism of N-phenyl-N′-(3,5-dimethylpyrazole-4-yl) thiourea in rats

Abstract

Thiourea derivatives have been shown to posses several biological activities. Therefore a series of N-substituted -N'-(3,5-di/1,3,5trimethylpyrazole-4-yl)thioureas were synthesized and the antitubercular and anticonvulsant activities were studied. Among the new compounds, N-phenyl-N'-(3,5-dimethylpyrazole4-yl)thiourea (S) was demonstrated to have remarkable anticonvulsant activity. In this study, S was selected as a model compound and the in vivo metabolic pathway in rats was investigated. The substrate was given intraperitoneally (50 mg/kg) and blood samples were collected at 0, 1, 2, 4, 8, 12, 24 and 48 h. The substrate and its potential metabolites were separated using HPLC on reverse phase system. The substrate was detected at all times with small quantity of metabolites.

High pressure liquid chromatographic analysis ofin vivo metabolites ofN(substituted phenyl)-N′-(1,3,5-trimethyl pyrazole-4-yl)thioureas in rats

“…General procedure for the preparation of NSubstituted-N'-(3,S-di/I,3,S-trimethylpyrazole-4-yl)thioureas (TI-T3) The intermediate products 4-amino-3,5-dime-thyVl, 3,5-trimethylpyrazole were prepared in 4 stages from aniline or ethyl 4-aminobenzoate according to the reported procedures (19). The intermedi-ate products (0.0085 mol in 100 ml anhydrous acetone) underwent reaction with appropriate isothio-cyanate (0.0085 mol) in anhydrous acetone (100 ml).…”

“…However, among the numerous studies reported, there are very few concerning the metabolism of thioureas (14)(15)(16)(17)(18). We therefore investigated the in vivo metabolism of N-phenyl-N-(3,5-dimethylpyrazole-4-y1)thiourea as a potent anticonvulsant a-'Please send reprint request to: Bedia Kocyigit-Kaymakcioglu, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Haydarpasa, 34668, istanbul, Turkey gent (19). In this investigation, the previous results had shown that the substrate was metabolized largely unchanged form in the plasma.…”

In vivo metabolism of 2-[1′-phenyl-3′-(3-chlorophenyl)-2′-propenylyden]hydraz ino-3-methyl-4(3H)-quinazolinone in rats

“…Plasma was prepared according to previously described methods [23,24]. One mL of cold acetonitrile-methanol (50:50 v/v) was added to 100 mL plasma to precipitate plasma proteins, and centrifuged at 6000 rpm for 10min.…”

A comparative study of the metal binding behavior of alanine based bis-thiourea isomers

“…Amongst this class of compounds, benzoyl derivatives of thiourea have gained a great deal of importance in the present day. Thiourea linkages have contributed greatly to the observed enhancement in various activities [3], including antiviral [4], antibacterial [5, 6], antifungal [7], antitubercular [8, 9], herbicidal [10], insecticidal [11], pharmacological properties [12], as chelating agents [13, 14] and as anticancer compounds [15]. In addition, benzoyl thiourea derivatives have often been used in analytical and biological applications [16, 17].…”