4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)phenyl]benzoicacid and heterocyclic-bridged analogues are novel retinoic acid receptor subtype and retinoid X receptor alpha agonists

Aromatic retinoids having a meta-substituted aromatic ring bridge, such as 4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)phenyl]benzoic acid and its 3,5-diaryl-substituted 4,5-dihydroisoxazole analogue, function as retinoid receptor panagonists by activating both retinoic acid and reti noid X receptors to induce gene transcription, and thereby provide novel sc affolds for retinoid drug development. Both classes of these ligand-inducib le transcription factors are involved in mediating the inhibitory effects o f retinoids on cancer cell growth. (C) 2000 Elsevier Science Ltd. All right s reserved.