NEW RAR RECEPTOR ACTIVATOR LIGANDS, USE IN HUMAN MEDICINES AND COSMETICS

摘要

1-Oxyalkoxy-substituted biaryl-prop-2-yn-1-ol compounds (I) are new. 1-Oxyalkoxy-substituted biaryl-prop-2-yn-1-ol compounds of formula (I), their optical and geometric isomers and salts of (I; R 1= OH), are new. Ar : 1,4-phenylene (optionally monosubstituted by R 7), pyridinediyl, thiophenediyl or furandiyl; R 1H, T, NR'R'' or OR 8; T : 1-6C alkyl; R 2H or T; R 3H, T or COR 9; R 4 + R 5a group completing a fused 5- or 6-membered ring (optionally substituted by Me and optionally interrupted by O or S); R 6T or COR 10; R 71-20C alkyl, alkenyl, mono- or poly-hydroxyalkyl, aryl or aralkyl (both optionally substituted) or sugar, aminoacid or peptide residue; R 9, R 10CF 3 or T; R 11H, T or COR 12; R 12T; R', R'' : H, T, mono- or poly-hydroxyalkyl, optionally substituted aryl or sugar, aminoacid or peptide residue, or NR'R'' : heterocyclyl, and n : 2-6. [Image] ACTIVITY : Dermatological; Antiseborrheic; Antiinflammatory; Antiallergic; Immunosuppressive; Antipsoriatic; Antirheumatic; Cytostatic; Virucide; Ophthalmological; Vulnerary; Anorectic; Antilipemic; Antidiabetic; Antiarthritic; Endodrine-Gen.; Antiasthmatic; Neuroprotective; Cardiant; Antiarteriosclerotic; Hypotensive. MECHANISM OF ACTION : Retinoic acid receptor (RAR) activator. In RAR transactivation tests in vitro in HeLa cells, 4-(3-hydroxy-3-(4-(2-ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-prop-1-ynyl)-2-hydroxybenzoic acid (Ia) had K d (apparent) of 30 nM and AC 50 of 150 nM for RARalpha receptors, K d (apparent) of 120 nM and AC 50 of 100 nM for RARbeta receptors and K d (apparent) of 1 nM and AC 50 of 1 nM for RARgamma receptors.