New biaromatic compounds are peroxisome proliferator-activated receptor modulators, useful to treat e.g. acnes, ichtyosis, psoriasis, eczema, verruca vulgaris, lupus erythematosus and scleroderma

摘要

Biaromatic compounds (I) and their salts, solvates and/or hydrates, are new. Biaromatic compounds of formula (I) and their salts, solvates and/or hydrates, are new. R1 : -OR6, -NR6-OR6 or -NR6R6; R2 : halo, 1-12C alkyl, -OR7, -NHR7 or aralkyl; R3 : 1-12C alkyl, 3-12C cycloalkyl or -(CH 2) mR8; X : -(CH 2) z-NR9-C(Y1)-(NR10) w-; m : 0-4; Y1 : S or O; z, w : 0-1; Ar1, Ar2 : aromatic radical (optionally substituted by R4 or R5) such as Ar1 is 1,3-diphenyl, pyridin-2,6-diyl, pyridin-2,4-diyl, pyridin-3,5-diyl, pyrimidin-2,4-diyl, pyrazin-2,6-diyl or pyrimidin-4,6-diyl and Ar2 may also be 1,4-diphenyl, pyridin-2,5-diyl, pyrimidin-2,5-diyl or pyrazin-2,5-diyl; R4, R5 : H, halo, 1-12C alkyl, OH, alkoxy, polyether, aralkyl, aryl or amino (optionally substituted by 1-2 radicals of 1-12C alkyl or aralkyl); R6 : H, 1-7C alkyl, aryl or aralkyl; R7 : H, 1-7C alkyl, aryl or aralkyl; R8 : 1-7C alkyl, cycloalkyl, aryl, aralkyl, heteroaryl or heterocycloalkyl, -OR11 or optionally substituted amino; R9, R10 : H or1-4C alkyl; and R11 : H, 1-7C alkyl, aryl or aralkyl. Independent claims are included for (1) a composition comprising (I) and an excipient; (2) a cosmetic composition comprising (I) in a support; and (3) the preparation of (I). [Image] ACTIVITY : Antiinflammatory; Dermatological; Antiseborrheic; Antipsoriatic; Antirheumatic; Antiallergic; Respiratory-Gen; Cytostatic; Virucide; Immunosuppressive; Nootropic; Anorectic; Metabolic; Cardiovascular-Gen.; Antiarthritic; Endocrine-Gen; Antiasthmatic; Immunostimulant; Immunomodulator; Antidiabetic; Neuroprotective; Antiarteriosclerotic; Hypotensive. MECHANISM OF ACTION : Peroxisome proliferator-activated receptor (PPAR) modulator. The potency of (I) in modulating PPAR receptor was tested in HeLN cells and was determined using the luminescence produced. The result showed that (Z)-2-ethoxy-3-{3'-[(methyl-octanoyl-amino)-methyl] -biphenyl-4-yl}-acrylic acid exhibited an apparent binding constant of 2000 nM.