ACONTINUED investigation of compounds which inhibit the function of the thyroid gland has revealed that appropriate substituents on the thiouracil molecule confer a greatly increased activity. The compounds 6-ethylthiouracil and 6-n propylthiouracil are among a group which are approximately ten times as active as thiouracil when tested in rats; compounds of this class have exhibited an activity far superior to any of some 300 thus far explored 2). Tests in rats have also shown that these derivatives exert a more lasting effect following a single dose than does thiouracil, a substance known to be rapidly eliminated from the body. These derivatives have the further therapeutic advantage of a greater activity-toxicity ratio; while they are more toxic than thiouracil on a weight basis they are considerably less toxic in acute and in chronic experiments when administered in quantities calculated on the basis of equivalent anti-thyroid effect. A selected group of the more effective anti-thyroid compounds when tested in chicks likewise showed that these thiouracils were much more active than any other compounds hitherto investigated (6).
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Astwood et al. (1945) studied this question.