Enantioselective syntheses of potent retinoid X receptor ligands: differential biological activities of individual antipodes.
Article Details
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Vuligonda V, Thacher SM, Chandraratna RA
Enantioselective syntheses of potent retinoid X receptor ligands: differential biological activities of individual antipodes.
J Med Chem. 2001 Jul 5;44(14):2298-303.
- PubMed ID
- 11428923 [ View in PubMed]
- Abstract
The synthesis and characterization of chiral RXR selective ligands are described. The enantiomeric acids 2 and 3 were synthesized employing an enantioselective cylopropanation procedure as the key step. Compound 2, with an S,S configuration at C-9 and C-10, is a potent RXR agonist devoid of any RAR activity. The R,R enantiomer 3 is a weak RXR agonist and has demonstrable RAR activity in the receptor transactivation assays. The potent RXR activity of 2 was further confirmed in a hyperglycemic animal model (db/db mice). Compound 2 lowered glucose by 50% by day 7 at 2 mg/kg, whereas 3 had no effect at the same dosage. This further supports the contention that RXR mediated gene transcription is involved in the antidiabetic effects of RXR ligands.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Tretinoin Retinoic acid receptor alpha EC 50 (nM) 21 N/A N/A Details Tretinoin Retinoic acid receptor alpha Kd (nM) 90 N/A N/A Details Tretinoin Retinoic acid receptor beta Kd (nM) 100 N/A N/A Details Tretinoin Retinoic acid receptor beta EC 50 (nM) 3 N/A N/A Details Tretinoin Retinoic acid receptor gamma EC 50 (nM) 4 N/A N/A Details Tretinoin Retinoic acid receptor gamma Kd (nM) 150 N/A N/A Details Tretinoin Retinoic acid receptor RXR-alpha EC 50 (nM) 1.5 N/A N/A Details Tretinoin Retinoic acid receptor RXR-alpha Kd (nM) 13 N/A N/A Details Tretinoin Retinoic acid receptor RXR-beta EC 50 (nM) 29 N/A N/A Details Tretinoin Retinoic acid receptor RXR-beta Kd (nM) 35 N/A N/A Details Tretinoin Retinoic acid receptor RXR-gamma Kd (nM) 30 N/A N/A Details Tretinoin Retinoic acid receptor RXR-gamma EC 50 (nM) 4.5 N/A N/A Details