Abstract: N-(4-Carboxy-phenyl)-3,5-di-t-butyl-4-hydroxy-benzamide (2) possesses structural prerequisite for cell-differentiation inducing activity, which constitutes the therapeutic basis of all-trans-retinoic acid (ATRA) and analogues for the treatment of cancer and dermatosis. In addition to the similarity of the disposition of functional groups with ATRA, 2 shows a conformational equivalence to ATRA in terms of molecular shape, size, as well as the spatial arrangement of functional groups. However, the N-methylated compound (3) is devoid of the activity. It owes the biological behavior to the conformational difference, because of the steric interference between N-methyl group and the hydrogen atom of a phenyl ring. X-ray crystallography, UV, and NMR were performed to investigate the difference.

Key words: Retinoids, Cell-differentiation inducing activity, Conformational equivalence