Abstract
Based on the examination of the X-ray crystallographic structures of the LBD of TRα and TRβ in complex with KB-141 ( 2), a number of novel 4′-hydroxy bioisosteric thyromimetics were prepared. Optimal affinity and β-selectivity (33 times), was found with a medium-sized alkyl-substituted amido group; iso-butyl ( 12c). It can be concluded that bioisosteric replacements of the 4′-hydroxy position represent a new promising class of TRβ-selective synthetic thyromimetics.
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