New 2-phenylthio-1,2,4-triazole derivatives are modulators of peroxisome proliferator activated receptors for treating e.g. skin diseases, tumors and cardiovascular disease

摘要

2-Phenylthio-1,2,4-triazole derivatives (I), are new. 2-Phenylthio-1,2,4-triazole derivatives of formula (I), their optical and/or geometric isomers, tautomers, N-oxides and salts are new. [Image] R1H, alkyl, aryl, heteroaryl or aralkyl; R2H, alkyl (optionally substituted by aryl or heteroaryl), CH2OR6 or aryl; R6aryl or heteroaryl; X : S, Se, O or NR7; R7H, alkyl, aralkyl or C(Y)R10; R3alkyl or aralkyl; R4hydroxy, alkoxy or NR8R9; R8, R9H or alkyl, or R8 + R9morpholino, piperidino or pyrrolidino; R5H, halo, alkyl, alkoxy or hydroxy; R10H, alkyl, alkoxy or NR11; R11H, alkyl or aralkyl; Y : O or S; n : 0-2, and m : 0 or 1, proviso that when X S or Se and m = 0, then n is 0 ACTIVITY : Dermatological; Antiseborrheic; Antiinflammatory; Immunosuppressive; Antipsoriatic; Virucide; Cytostatic; Antilipemic; Anorectic; Antidiabetic; Antiarthritic; Antiasthmatic; Antiarteriosclerotic; Hypotensive. MECHANISM OF ACTION : Peroxisome proliferator-activated receptor (PPAR) modulator. In a test, results showed that (4-[4-[5-(4-tert-butylphenyl)-4-methyl-4H-[1,2,4]triazol-3-sulfanyl]-2-heptyloxybenzylamino]phenyl)acetic acid exhibited an apparent dissociation constant of 8000 nM for PPARalpha and 15 nM for PPARgamma .