title: Diphenylamine-based retinoid antagonists: regulation of RAR and RXR function depending on the N-substituent.
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.
authors: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Aoba-ku, Sendai, Japan.
authors: Kiminori
authors: K
authors: Ohta
authors: Emiko
authors: E
authors: Kawachi
authors: Hiroshi
authors: H
authors: Fukasawa
authors: Koichi
authors: K
authors: Shudo
authors: Hiroyuki
authors: H
authors: Kagechika
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D004159:Diphenylamine / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D047488:Retinoid X Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012176:Retinoids / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D004159:Diphenylamine