Enantioselective syntheses of potent retinoid X receptor ligands: differential biological activities of individual antipodes.

Article Details

Citation
Copy to clipboard

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
DrugTargetPropertyMeasurementpHTemperature (°C)
TretinoinRetinoic acid receptor alphaEC 50 (nM)21N/AN/ADetails
TretinoinRetinoic acid receptor alphaKd (nM)90N/AN/ADetails
TretinoinRetinoic acid receptor betaKd (nM)100N/AN/ADetails
TretinoinRetinoic acid receptor betaEC 50 (nM)3N/AN/ADetails
TretinoinRetinoic acid receptor gammaEC 50 (nM)4N/AN/ADetails
TretinoinRetinoic acid receptor gammaKd (nM)150N/AN/ADetails
TretinoinRetinoic acid receptor RXR-alphaEC 50 (nM)1.5N/AN/ADetails
TretinoinRetinoic acid receptor RXR-alphaKd (nM)13N/AN/ADetails
TretinoinRetinoic acid receptor RXR-betaEC 50 (nM)29N/AN/ADetails
TretinoinRetinoic acid receptor RXR-betaKd (nM)35N/AN/ADetails
TretinoinRetinoic acid receptor RXR-gammaKd (nM)30N/AN/ADetails
TretinoinRetinoic acid receptor RXR-gammaEC 50 (nM)4.5N/AN/ADetails