Inhibition of iodothyronine 5′‐deiodinase by thioureylenes; Structure‐activity relationship

Abstract

Thicrurea derived compounds are known for Pheii goitrogenic activity [I]. These substances block the biosynthesis of thyroxine (T,) by inhibiting thyroid peroxidase [Z]. Among them rare the 2-bhiouracil (TU) derivatives, which have an additional inhibitory zffect on the deiodinactive metabolism of tky)iroid hormone in peripheral tissues [3,4]. T4 is considered as a prohormone, which is converted into the biologically active form of thyroid hormone, 3,3',5triiodothyronine (T,), by the enzyme iodothyronine 5'deiodinase [5]. Deiodination of Tq may also yield the inactive rnetabolite 3,3'.5'-triiodothyronine (rT3). This latter reaction is probably mediated by a second enzyme, iodothyronine 5-deiodinase 151. The main pathway of rT; degradation is by 5'-deiodination into 3,3'-diiodothyronine [511. The latter may also be poduced by 5-deiodination of T, 151: