New 4-phenyliminoethoxy-benzoic acid derivatives are activating ligands for nuclear retinoic acid receptors used for treating skin diseases and in cosmetics

摘要

4-(2-Phenyl-2-iminoethoxy)benzoic acid derivatives (I), are new. 4-(2-Phenyl-2-iminoethoxy)benzoic acid derivatives of formula (I), their salts and optical and geometric isomers, are new. [Image] R 1OH, OR 7 or NR 8R 9; R 2H, F, Cl, 1-3C alkyl, hydroxy or OR 10; R 3H, Me, Et, isopropyl, tert-butyl or trifluoromethyl; R 4H, F, Cl, OR 11, Me, Et, isopropyl, tert-butyl or trifluoromethyl; R 5, R 6H, Me, Et, n-propyl, isopropyl, tert-butyl or COR 12, or R 5 + R 6piperidine, pyrrolidine, morpholine, pyrrolidin-2-one or piperid-2-one (all optionally substituted by at least 1 Me, Et, F or Cl); Q : OH, OR 13, NR 14R 15 or SO 2R 16; X-Y : CONH, CH 2O, CH 2S, CH 2NR 17, CH 2CH 2 or -CH=CH-; R 71-20C alkyl, alkenyl, mono- or poly-hydroxyalkyl, aryl, aralkyl (optionally substituted) or a sugar residue; R 8, R 9H, hydroxy, 1-6C alkyl, mono- or poly-hydroxyalkyl, aryl (optionally substituted) or complete the residue of an amino acid or peptide, or R 8 + R 9piperidine, pyrrolidine, morpholine, pyrrolidin-2-one or piperid-2-one; R 101-6C alkyl; R 111-6C alkyl or a mono- or poly-ether group; R 121-6C alkyl or OR 18; R 131-15C alkyl; R 14, R 15H, 1-6C alkyl or COR 19; R 16, R 18, R 191-6C alkyl, and R 17H, 1-6C alkyl or trifluoromethyl. Independent claims are also included for pharmaceutical and cosmetic compositions containing (I). ACTIVITY : Dermatological; Antiinflammatory; Antiallergic; Cytostatic; Ophthalmological; Virucide; Antiseborrheic; Vulnerary. MECHANISM OF ACTION : Nuclear retinoic acid receptor (RAR) activating ligand. In tests, results showed that 4-[2-(3-tert-butyl-4-diethylaminophenyl)-2-hydroxyiminoethoxy]benzoic acid (Ia) has apparent dissociation constants of 500 and 60 nM for RARbeta and RARgamma , respectively, with corresponding concentrations for 50% activation of 2500 nM and 80 nM.