SYNTHESIS AND ANTITHYROID ACTIVITY OF 1,4,5-TRIALKYL 2-THIOIMIDAZOLE DERIVATIVES

A series of compounds based on the structure of MTI (1-methyl-2-thioim idazole) were synthesized by condensation of alpha-hydroxyketones and alkylthioureas. The alpha-hydroxyketones were obtained by a radical re action in the presence of sodium and the alkyl ester, while the alkylt hioureas were prepared by nucleophilic addition of ammonia on an alkyl isothiocyanate. The antithyroid activity of the 13 compounds prepared was evaluated in vitro by determination of the concentrations which le d to a 50% inhibition (IC50) of the activity of thyroid peroxidase, an d in vivo by assay of thyroid hormones levels and histological examina tion of the thyroid gland in rats treated chronically with the compoun ds. 1-methyl-4,5-dipropyl 2-thioimidazole (compound 10) was found to h ave the highest antithyroid activity of the 13 compounds synthesized.