SYNTHESIS AKD BIOLOGICAL ACTIVITY OF SOME TRIIODINATED ANALOGUES OF THYROXINE* BY KEXKICHI TOMITAt

Although it has been clearly established that thyroxine is the main circulating form of the thyroid hormone (1, 2), there is some evidence in favor of the view that it must be converted to some other substance before it is fully effective in peripheral tissues. Among these points of evidence are (a) t.he lag period between thyroxine administration and a detectable response in basal metabolic rate; (b) the fact that the biological activity of certain analogues of thyroxine is not depressed by compounds antagonistic to thyroxine (3, 4); and (c) the more rapid response of human subjects to triiodothyronine (5, 6), a compound to which thyroxine is converted by non-thyroidal tissue (7, 8). It has therefore been considered of importance to prepare additional new analogues of thyroxine in the hope t.hat furt.her information might be gained about t,he nature of the cellularly active form of the hormone and about the minimal structural requirements for activity. Special attention has been given to the preparation of triiodinated compounds to determine whether the differences in biological activity of the Ia and 1, compounds in the thyronines are exhibited also in the thyronamine, thyraniline, and thyroxylic acid series.1 The compounds synthesized were tested to determine their effect on tadpole metamorphosis, basal metabolic rate of intact rats, and goiter prevention in thiouracil-fed rats. Their effects on enzyme systems in tr’tro will be described elsewhere.