9-cis-retinoic acid analogues with bulky hydrophobic rings: new RXR-selective agonists.

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Alvarez R, Vega MJ, Kammerer S, Rossin A, Germain P, Gronemeyer H, de Lera AR

9-cis-retinoic acid analogues with bulky hydrophobic rings: new RXR-selective agonists.

Bioorg Med Chem Lett. 2004 Dec 20;14(24):6117-22.

PubMed ID
15546741 [ View in PubMed
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Abstract

Stille cross-coupling of aryltriflates 10 and dienylstannane 11, oxidation and Horner-Wadsworth-Emmons reaction afforded stereoselectively retinoates 15. Saponification provided the carboxylic acids 8a and 8b, retinoids that incorporate a bulky hydrophobic ring while preserving the 9-cis-geometry of the parent system. In contrast to the pan-RAR/RXR agonistic profile of the lower homologue of 8a, compound 7 (LG100567), retinoids 8 showed selective binding and transactivation of RXR, devoid of significant RAR activation. In PLB985 leukemia cells that require RXR agonists for differentiation compounds 8 induced maturation in the presence of the RAR-selective pan-agonist TTNPB; this effect was blocked by an RXR-selective antagonist.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Arotinoid acidRetinoic acid receptor betaProteinHumans
Unknown
Not AvailableDetails