As commonly depicted, in the
thione form, thionamides (including
thiourea and its derivatives) bear little resemblance to
thyroid hormone. However, if placed in the
thiol resonance form, these molecules are noted to structurally mimic the end of the
tyrosine molecule (the precursor of
thyroid hormone). Alternatively,
tyrosine written in the -one configuration resembles the thionamides. This permits a better appreciation of why the thionamides may themselves be iodinated by
thyroid peroxidase in some cases, and under other circumstances induce changes in the
enzyme. The
thiol resonant form can be written for naturally occurring
goitrin, and for thiobarbituric
acids with antithyroid activity. An
hydroxyl resonant configuration can be drawn for the antithyroid compound
3-hydroxy-4-pyridone.
Tetramethylthiourea is a thyroid
carcinogen in rats. The compound can not be readily placed in the
thiol resonant configuration; it also contains 2 methyl groups at both ends of the molecule. The
hair dye 2,4-diaminoanisole sulfate induces
thyroid neoplasms in rats. A similarity is pointed out both to
tyrosine an to lower potency antithyroid aminobenzenes (described by Astwood and coworkers).
Pyrazole, known to produce thyroid
necrosis, is seen to have a distinct resemblance to the opposite end of several of these compounds.