Thyroid receptor ligands. Part 4: 4′-amido bioisosteric ligands selective for the thyroid hormone receptor beta

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作者：

YL Li，C Litten，KF Koehler，Karin Mellstr?m，N Garg，AMG Collazo，Mathias F?rneg?rd，M Grynfarb，B Husman，J Sandberg

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摘要：

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

carboxylic acids (benzene compounds) phenol ethers receptor binding activity

DOI：

10.1016/j.bmcl.2005.11.002

被引量：

年份：

2006