Discovery of a novel series of 6-azauracil-based thyroid hormone receptor ligands: potent, TR beta subtype-selective thyromimetics.
Article Details
- CitationCopy to clipboard
Dow RL, Schneider SR, Paight ES, Hank RF, Chiang P, Cornelius P, Lee E, Newsome WP, Swick AG, Spitzer J, Hargrove DM, Patterson TA, Pandit J, Chrunyk BA, LeMotte PK, Danley DE, Rosner MH, Ammirati MJ, Simons SP, Schulte GK, Tate BF, DaSilva-Jardine P
Discovery of a novel series of 6-azauracil-based thyroid hormone receptor ligands: potent, TR beta subtype-selective thyromimetics.
Bioorg Med Chem Lett. 2003 Feb 10;13(3):379-82.
- PubMed ID
- 12565933 [ View in PubMed]
- Abstract
In this communication, we wish to describe the discovery of a novel series of 6-azauracil-based thyromimetics that possess up to 100-fold selectivities for binding and functional activation of the beta(1)-isoform of the thyroid receptor family. Structure-activity relationship studies on the 3,5- and 3'-positions provided compounds with enhanced TR beta affinity and selectivity. Key binding interactions between the 6-azauracil moiety and the receptor have been determined through of X-ray crystallographic analysis.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 2-[4-(4-Hydroxy-3-Isopropyl-Phenoxy)-3,5-Dimethyl-Phenyl]-2h-[1,2,4]Triazine-3,5-Dione Thyroid hormone receptor beta Ki (nM) 0.03 N/A N/A Details Liothyronine Thyroid hormone receptor alpha EC 50 (nM) 2 N/A N/A Details Liothyronine Thyroid hormone receptor beta EC 50 (nM) 2 N/A N/A Details Liothyronine Thyroid hormone receptor beta Ki (nM) 0.08 N/A N/A Details