Thyroid receptor ligands. Part 8: Thyromimetics derived from N-acylated-alpha-amino acid derivatives displaying modulated pharmacological selectivity compared with KB-141.
Article Details
- CitationCopy to clipboard
Garg N, Li YL, Garcia Collazo AM, Litten C, Ryono DE, Zhang M, Caringal Y, Brigance RP, Meng W, Washburn WN, Agback P, Mellstrom K, Rehnmark S, Rahimi-Ghadim M, Norin T, Grynfarb M, Sandberg J, Grover G, Malm J
Thyroid receptor ligands. Part 8: Thyromimetics derived from N-acylated-alpha-amino acid derivatives displaying modulated pharmacological selectivity compared with KB-141.
Bioorg Med Chem Lett. 2007 Aug 1;17(15):4131-4. Epub 2007 May 21.
- PubMed ID
- 17543524 [ View in PubMed]
- Abstract
Based on the scaffold of the pharmacologically selective thyromimetic 2b, structurally a close analog to KB-141 (2a), a number of novel N-acylated-alpha-amino acid derivatives were synthesized and tested in a TR radioligand binding assay as well as in a reporter cell assay. On the basis of TRbeta(1)-isoform selectivity and affinity, as well as affinity to the reporter cell assay, 3d was selected for further studies in the cholesterol-fed rat model. In this model 3d revealed an improved therapeutic window between cholesterol and TSH lowering but decreased margins versus tachycardia compared with 2a.
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 alpha EC 50 (nM) 1.7 7 4 Details KB-141 Thyroid hormone receptor beta IC 50 (nM) 1.1 7 4 Details KB-141 Thyroid hormone receptor beta EC 50 (nM) 0.78 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