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

作者：Ohta Kiminori; Kawachi Emiko; Fukasawa Hiroshi; Shudo Koichi; Kagechika Hiroyuki^*

来源：Bioorganic & Medicinal Chemistry, 2011, 19(8): 2501-2507.

DOI：10.1016/j.bmc.2011.03.026

• Retinoid
• RAR
• Antagonist
• Diphenylamine

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 x 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.

• 出版日期2011-4-15
• 单位河北医科大学