Antithyroid activity of thiohydantoins

The antithyroid activity of 2-thiohydantoin and some derivatives has been measured in rats, after a single dose and, also, after daily administration for 6 weeks. 2-Thiohydantoin and its 5-alkyl derivatives from 5-methyl to 5-sec-butyl- showed considerable antithyroid activity at a dose of 0.05 m.mole/kg. by mouth, but 5-n-hexyl-2-thiohydantoin had insignificant activity at this dose level. The presence of polar groups in the 5-substituent was associated with reduction or complete loss of activity. By the single-dose technique, 2-thiohydantoin was more potent than its 5-alkyl derivatives. The opposite result was obtained by other methods of assessment after 42 days of treatment. Some of the possible factors involved are discussed especially in relation to the difficulty of comparing results obtained by the different methods of assessment. The acute toxicity of 2-thiohydantoin and of its 5-methyl and 5-ethyl derivatives is reported. No toxic effects were found after daily administration of several 2-thiohydantoins at a dose of 50 mg./kg. for 6 weeks.