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

• Published in: Bioorganic & medicinal chemistry letters Vol. 10; no. 12; pp. 1311 - 1313
• Main Authors: Dawson, Marcia I, Jong, Ling, Hobbs, Peter D, Xiao, Dongmei, Feng, Kai-Chia, Chao, Wan-ru, Pan, Chin, Fontana, Joseph A, Zhang, Xiao-kun
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 19.06.2000; Elsevier
• Subjects: Antineoplastic agents; Benzoates - chemistry; Benzoates - pharmacology; Biological and medical sciences; General aspects; Heterocyclic Compounds - chemistry; Heterocyclic Compounds - pharmacology; Humans; Medical sciences; Naphthalenes - chemistry; Naphthalenes - pharmacology; Pharmacology. Drug treatments; Receptors, Retinoic Acid - agonists; Retinoid X Receptors; Transcription Factors - agonists; Tumor Cells, Cultured; Antineoplastic agent; Human; Agonist; Nuclear receptor; Isoxazole derivatives; Benzene derivatives; Retinoid; Cytotoxicity; Selectivity; Epithelium; In vitro; Naphthalene derivatives; Cell line; Structure activity relation; Carboxylic acid; Breast; Affinity; Mammary gland; Chemical synthesis; Tumor cell; Oxygen nitrogen heterocycle; Biological receptor
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(00)00244-4

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 retinoid X receptors to induce gene transcription, and thereby provide novel scaffolds for retinoid drug development. Both classes of these ligand-inducible transcription factors are involved in mediating the inhibitory effects of retinoids on cancer cell growth.