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Structure-activity relationship study on benzoic acid part of diphenylamine-based retinoids
Kiminori Ohta1, Emiko Kawachi, Koichi Shudo
1Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
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.
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