1 2 3 4 Tetrahydroisoquinolines derivatives as urotensin II receptor antagonists

Compounds of the general formula 1,

• 55
• wherein
• X represents —CH2—, CH2CH2—, —C(CH3)2;
• Y represents oxygen, NH;
• n represents the numbers 1 or 2;
• Z represents quinolin-4-yl which may be mono-substituted with lower alkyl in the positions 2, 6, or 8, or di-substituted with lower alkyl in the positions 2, 6 or 2,8;
• [1,8]naphthyridin-4-yl which may be substituted in position 7 with lower alkyl;
• pyridin-4-yl which may be substituted in position 2 with R7R8N— and additionally in position 6 with hydrogen or lower alkyl;
• R1 represents naphthalen-1-yl;
• naphthalen-2-yl;
• benzo[1,3]dioxol-5-yl;
• benzyl, or mono-, di-, or tri-substituted benzyl substituted in the phenyl ring independently with lower alkyl, lower alkyloxy, trifluoromethyl, halogen, cyano;
• phenyl, or mono-, di- or tri-substituted phenyl, substituted independently with lower alkyl, lower alkyloxy, trifluoromethyl, halogen, cyano;
• R2 represents hydrogen, lower alkyl, aryl or forms with R1 a styryl group of E or Z geometry, whereby the phenyl ring in the styryl group may be mono-, di- or tri-substituted phenyl, substituted independently with lower alkyl, lower alkyloxy, trifluoromethyl, halogen, cyano;
• R3, R4, R5 and R6 independently represent hydrogen, cyano, hydroxy, lower alkyloxy, aralkyloxy, lower alkenyloxy, and R5 additionally represents R7R8NCO;
• R4 and R5 together may form with the phenyl ring a five- or a six-membered ring containing one or two oxygen atoms;
• R7 and R8 independently represent hydrogen, lower alkyl, aryl, aralkyl, or together with the N form a pyrrolidine, piperidine, or morpholine ring;
• and optically pure enantiomers or diastereomers, mixtures of enantiomers or diastereomers, diastereomeric racemates, and mixtures of diastereomeric racemates;
• as well as their pharmaceutically acceptable salts, solvent complexes, and morphological forms.