New (thio)ureido biaryls are perioxisome proliferator-activated gamma receptor subtype activators, useful for treating e.g. dermatological diseases, cardiovascular diseases and cancer

摘要

(Thio)ureido biaryls (I) are new. (Thio)ureido biaryls of formula (I) and their salts are new. R 1OH, OR 6 or hydroxylamine radical; R 2, R 3, R 7 and R 8amino (optionally mono or disubstituted by 1-12C alkyl or aralkyl), H, halo, 1-12C alkyl, OH, alkoxy, polyether, aralkyl or aryl; R 4H or 1-4C alkyl; R 51-12C alkyl, aryl, aralkyl, heteroaryl or heterocyclic; R 6alkyl, aryl or aralkyl; Y : O or S; and V-W : single or double carbon-carbon bond i.e. sequence -CH 2-CH 2- or -CH=CH-. Independent claims are also included for the following: (1) a pharmaceutical composition comprising (I) in a support; and (2) a cosmetic composition comprising (I). [Image] ACTIVITY : Dermatological; Antiseborrheic; Antipsoriatic; Antiinflammatory; Virucide; Cytostatic; Immunosuppressive; Keratolytic; Vulnerary; Radioprotective; Anorectic; Antidiabetic; Antilipemic; Antiarthritic; Endocrine-Gen; Antiasthmatic; Cardiovascular-Gen; Antiarteriosclerotic; Neuroprotective; Hypotensive; Immunomodulator; Antirheumatic; Antiallergy; Antilichen; Respiratory-Gen. MECHANISM OF ACTION : Perioxisome proliferator-activated receptor-gamma (PPAR-gamma ) activator. HeLN cells containing plasmids ERE-beta -Glob-Luc-SC-Neo (reporter gene) and PPAR (alpha /beta /gamma )Gal-h-PPA, were incubated with 3-[3'-(3-heptyl-1-methylureido)-2-propoxybiphenyl-4-yl]propanoic acid (Ia), DMEM medium without phenol red and supplemented with 10% of deflated calf serum, at 37[deg]C along with 7% carbon dioxide for 16 hours. (Ia) Was found to have a K d value of 0.25/120/500 (nM) for PPAR-gamma /beta /alpha receptor subtypes respectively.