Retinoic acid receptor beta,gamma-selective ligands: synthesis and biological activity of 6-substituted 2-naphthoic acid retinoids.

Article Details

Citation

Yu KL, Spinazze P, Ostrowski J, Currier SJ, Pack EJ, Hammer L, Roalsvig T, Honeyman JA, Tortolani DR, Reczek PR, Mansuri MM, Starrett JE Jr

Retinoic acid receptor beta,gamma-selective ligands: synthesis and biological activity of 6-substituted 2-naphthoic acid retinoids.

J Med Chem. 1996 Jun 7;39(12):2411-21.

PubMed ID
8691435 [ View in PubMed
]
Abstract

In search for retinoic acid receptor (RAR) selective ligands, a series of 6-substituted 2-naphthoic acid retinoids were synthesized and evaluated in vitro in a transactivation assay and a competition binding assay for all RARs. These derivatives, in general, showed RAR beta,gamma selectivity. Among these naphthoic acids, oxime derivative 12 was identified as a potent RAR gamma-selective retinoid, while olefinic derivative 11 was found to be comparable to retinoic acid and slightly RAR beta,gamma selective. For the bioassays, a general correlation was observed between the binding affinity of the ligand to the receptors and the potency of the compounds in the transactivation assay. The structure-activity relationship of these naphthoic acids will be discussed.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
BMS184394Retinoic acid receptor gammaKd (nM)75N/AN/ADetails
CD564Retinoic acid receptor gammaKd (nM)3N/AN/ADetails
SR11254Retinoic acid receptor gammaKd (nM)3.3N/AN/ADetails
TretinoinRetinoic acid receptor alphaKd (nM)2.3N/AN/ADetails
TretinoinRetinoic acid receptor betaKd (nM)0.4N/AN/ADetails
TretinoinRetinoic acid receptor gammaKd (nM)0.3N/AN/ADetails