SUBSTITUTED OXINDOLE DERIVATIVES AND THEIR USE AS VASOPRESSIN RECEPTOR LIGANDS

摘要

Disclosed is a compounds of the general formula (I) in which R5 is hydrogen, methoxy or ethoxy; R6 is hydrogen or methoxy; R7 is hydrogen, methyl, ethyl, n-propyl or isopropyl; X2 is N or CH; X3 is N or CH; and where X2 and X3 are not simultaneously N; and the pharmaceutically acceptable salts, tautomeric forms and prod rugs thereof. Also disclosed are a medicament comprising a compound of formal (I) ; a pharmaceutical composition comprising a compound of formula (I) and the use of a compound of formula (I) in the manufacture of a medicament for treating at least one vasopressin-dependent disease, diabetes, insulin resistance, nocturnal enuresis, incontinence, diseases in which blood coagulation disorders occur, and/or for delaying micturition, hypertension, pulmonary hyper-tension, heart failure, myocardial infarction, coronary spasm, unstable angina, PTCA (percutaneous transluminal coronary angioplasty), ischemias of the heart, disorders of the renal system, edemas, renal vasospasm, necrosis of the renal cortex, hyponatremia, hypokalemia, Schwartz-Bartter syndrome, disorders of the gastrointestinal tract, gastritic vasospasm, hepatocirrhosis, gastric and intestinal ulcer, emesis, emesis occurring duringchemotherapy, and/or travel sickness. Examples of compound include N-[5-Cyano-1-[(2, 4-dimethoxyphenyl)sulphonyl} -3-(2-ethoxypyridin-3-yl)-2-oxo-2,3-dihydro-1 H-indol-3-yl} -4-(1-methylpiperidin-4-yl)piperazine-1-carboxamide; (+)-N-[5-Cyano-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-ethoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-(1-methylpiperidin-4-yl)piperazine-1-carboxamide and (-)-N-[5-Cyano-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-ethoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-(1-methylpiperidin-4-yl)piperazine-1-carboxamide.