New 1-sulfonyl-2-oxo-dihydroindole derivatives are selective antagonists of vasopressin receptors useful e.g. for treating hypertension, cardiac insufficiency, unstable angina or affective disorders

摘要

1-sulfonyl-2-oxo-2,3-dihydroindole derivatives (I) and their tautomers, enantiomers and/or diastereomers, prodrugs and salts are new. 1-sulfonyl-2-oxo-2,3-dihydroindole derivatives of formula (I) and their tautomers, enantiomers and/or diastereomers, prodrugs and salts are new. A : 6-10C aryl (optionally substituted); B : (partially) aromatic 6-10C mono- or bi-cyclic residue (optionally substituted); R 1H, 1-6C alkyl, OH, 1-4C alkoxy, di(1-4C alkyl)amino, CN, carbamoyl, trifluoromethoxy, trifluoromethyl, bromo, fluoro, chloro, iodo, nitro, formamido, 1-4C alkylcarbonylamino or ureido; R 2H, 1-4C alkyl, 1-4C alkoxy, chloro or fluoro; R 3W-X-Y-Z; W : 1-4C alkylene, (0-4C alkylene)-O-(0-4C alkylene) or (0-4C alkylene)-NR 15-(0-4C alkylene); R 15H or 1-4C alkyl; X : CO, SO 2, C=NH or C=N-CN; Y : e.g. pyrrolidindiyl, piperazindiyl or piperidindiyl (optionally substituted); and Z : e.g. pyrrolidinyl, azepinyl or morpholino. The full definitions are given in the DEFINITIONS (Full Definitions) field. An independent claim is also included for two methods for preparing (I). [Image] ACTIVITY : Uropathic; Antithrombotic; Anticoagulant; Hypotensive; Cardiant; Antianginal; Antiischemic; Nephrotropic; Antiinflammatory; Antidiuretic; Hepatotropic; Antiulcer; Antiemetic; Antidepressant; Tranquilizer; Nootropic; Neuroprotective. MECHANISM OF ACTION : Vasopressin receptor antagonist, e.g. V 1a and V 1b receptor antagonist. N-(1-(2,4-dimethoxybenzenesulfonyl-5-chloro-2-oxo-3-(2-methoxyphenyl)-2,3-dihydro-1H-indol-3-yl) 4-(1-methylpiperidin-4-yl)-piperazine-1-carboxamide dihydrochloride (Ia) had affinity constant for the V 1a receptor below 100 nM, when tested by the method of Br. J. Pharmacol., 125 (1998) 1463.