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

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Li YL, Litten C, Koehler KF, Mellstrom K, Garg N, Garcia Collazo AM, Farnegard M, Grynfarb M, Husman B, Sandberg J, Malm J

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

Bioorg Med Chem Lett. 2006 Feb 15;16(4):884-6. Epub 2005 Nov 21.

PubMed ID
16303304 [ View in PubMed
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Abstract

Based on the examination of the X-ray crystallographic structures of the LBD of TRalpha and TRbeta in complex with KB-141 (2), a number of novel 4'-hydroxy bioisosteric thyromimetics were prepared. Optimal affinity and beta-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 TRbeta-selective synthetic thyromimetics.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
KB-141Thyroid hormone receptor alphaIC 50 (nM)2574Details
KB-141Thyroid hormone receptor betaIC 50 (nM)1.174Details
LiothyronineThyroid hormone receptor alphaIC 50 (nM)0.2474Details
LiothyronineThyroid hormone receptor betaIC 50 (nM)0.2674Details