Thyroid receptor ligands. Part 5: Novel bicyclic agonist ligands selective for the thyroid hormone receptor β

Based on the examination of the crystal structure of rat TRβ complexed with 3,5,3′-triiodo-l-thyronine (2) a novel TRβ-selective indole derivative 6b was prepared and tested in vitro. This compound was found to be 14 times selective for TRβ over TRα in binding and its β-selectivity could be rationalized through the comparison of the X-ray crystallographic structures of 6b complexed with TRα and TRβ.

Graphical abstractBased on the examination of the crystal structure of rat TRβ complexed with 3,5,3′-triiodo-l-thyronine (2), a novel TRβ-selective indole derivative 6b was prepared and tested in vitro. Its β-selectivity could be rationalized through the comparison of the X-ray crystallographic structures of 6b complexed with TRα and TRβ.Figure optionsDownload full-size imageDownload as PowerPoint slide