Bioorganic & Medicinal Chemistry Letters 2013-01-01

Structure-activity relationship study on benzoic acid part of diphenylamine-based retinoids.

Kiminori Ohta, Emiko Kawachi, Koichi Shudo, Hiroyuki Kagechika

Index: Bioorg. Med. Chem. Lett. 23(1) , 81-4, (2013)

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Abstract

Based on structure-activity relationship studies of the benzoic acid part of diphenylamine-based retinoids, the potent RXR agonist 4 was derivatized to obtain retinoid agonists, synergists, and an antagonist. Cinnamic acid derivatives 5 and phenylpropionic acid derivatives 6 showed retinoid agonistic and synergistic activities, respectively. The difference of the activities is considered to be due to differences in the flexibility of the carboxylic acid-containing substituent on the diphenylamine skeleton. Compound 7, bearing a methyl group at the meta position to the carboxyl group, was an antagonist, dose-dependently inhibiting HL-60 cell differentiation induced by 3.3 × 10(-10)M Am80.Copyright © 2012 Elsevier Ltd. All rights reserved.