EXCRETION STUDIES ON THIOURACIL AND ITS 6-BENZYL, 6-n-PROPYL AND 6-METHYL DERIVATIVES IN MAN*

Abstract

AMONG the derivatives of thiouracil studied quantitatively by Astwood, Bissell and Hughes (1) for antithyroid activity in rats, 6-benzylthiouracil was found to be one of the most active compounds. On the basis of reduction in thyroid iodine concentration and to a lesser extent on the degree of thyroid enlargement following administration of the drug in the diet for ten days, benzylthiouracil was estimated to be 10 times as active as thiouracil and only slightly less potent than propylthiouracil. Methylthiouracil was estimated to be equal in potency to thiouracil. Quantitative evaluation of certain goitrogens by McGinty et al. (2) based on the capacity of these substances to inhibit collection of radioiodine following single injections into rats, indicated that benzylthiouracil and propylthiouracil were approximately 10 times as active as thiouracil and methylthiouracil. These studies appeared to be quite consistent with those in which comparative potency was established by the chronic feeding tests. However, similar studies using chicks instead of rats showed that benzylthiouracil was considerably more active than propylthiouracil or thiouracil, the latter two possessing about equal inhibitory effects on uptake of radioiodine by the chick thyroid. Methylthiouracil was not included in the chick studies.