5,6-Disubstituted oxindole derivatives and their use in the manufacture of a medicament for the treatment of vasopressin-dependent diseases

摘要

5,6-Disubstituted oxindole-derivatives (I) and their salts or prodrugs, are new. 5,6-Disubstituted oxindole-derivatives of formula (I) and their salts or prodrugs, are new. R 1>, R 2>H, 1-3C-alkyl, 1-3C-fluoroalkyl, 1II-3C-alkoxy, 1-3C-fluoroalkoxy, halo or CN; R 3>H or 1-4C-alkyl; R 4>ethoxy, fluorinated ethoxy or isopropoxy; R 5>H or CH 3; R 6>Br, Cl, F or CN; R 7>Cl, F or CN; R 8>, R 9>1-3C-alkyl or 1-3C-fluoroalkyl; X 1>O, NH or CH 2; X 2>-X 4>N or CH; a, b : 0-2; and m, n, o, p : 1-3. Provided that X 2>and X 3>are not simultaneously N [Image] ACTIVITY : Antidiabetic; Uropathic; Hypotensive; Cardiant; Antianginal; Vasotropic; Nephrotropic; Antiinflammatory; Metabolic; Endocrine-Gen.; Gastrointestinal-Gen.; Hepatotropic; Antiemetic; Antidepressant; Tranquilizer; Nootropic; Neuroprotective; Neuroleptic; Hypnotic; Antiaddictive; Gynecological; Antipyretic. MECHANISM OF ACTION : Vasopressin receptor modulator. The ability of (I) to modulate vasopressin 1b receptor was tested in Chinese hamster ovary cells (CHO-K1). The results showed that 4-(1-methyl-piperidin-4-yl)-piperazin-1 -carboxylic acid-[5-cyano-1 -(2,4-dimethoxyphenylsulfonyl)-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indol-3-yl]-amide exhibited a dissociation constant of less than 1 nM.