Thyroid receptor ligands. Part 4: 4'-amido bioisosteric ligands selective for the thyroid hormone receptor beta.
Article Details
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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]
- 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
Drug Target Property Measurement pH Temperature (°C) KB-141 Thyroid hormone receptor alpha IC 50 (nM) 25 7 4 Details KB-141 Thyroid hormone receptor beta IC 50 (nM) 1.1 7 4 Details Liothyronine Thyroid hormone receptor alpha IC 50 (nM) 0.24 7 4 Details Liothyronine Thyroid hormone receptor beta IC 50 (nM) 0.26 7 4 Details