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ID: ALA1764950

Journal: Bioorg Med Chem

Title: Diphenylamine-based retinoid antagonists: regulation of RAR and RXR function depending on the N-substituent.

Authors: Ohta K, Kawachi E, Fukasawa H, Shudo K, Kagechika H.

Abstract: Based upon the structure-activity relationships of diphenylamine derivatives with retinoid synergistic activity (RXR agonists), novel diphenylamine derivatives with a long alkyl chain (9a and 9b) or a benzyl group (10a-f) as the N-substituent were designed and synthesized. All the synthesized compounds dose-dependently inhibited HL-60 cell differentiation induced by 3.3×10(-10)M Am80. Among them, compound 10f showed the most potent inhibitory activity, and the mechanism was shown, by means of transactivation assay for RARs and RXRs, to involve antagonism against RARs. The N-substituent of the diphenylamine skeleton plays an important role in determining the receptor selectivity for RARs or RXRs, as well as the agonist or antagonist nature of the activity.

CiteXplore: 21459577

DOI: 10.1016/j.bmc.2011.03.026