A method of treating a patient for a condition selected from stable or unstable angina pectoris, coronary heart disease, coronary artery disease, Prinzmetal angina, acute coronary syndrome, cardiac insufficiency, heart failure, myocardial infarction, stroke, thrombosis, peripheral artery occlusive disease, endothelial dysfunction, atherosclerosis, restenosis, endothelial damage after PTCA, hypertension, essential hypertension, pulmonary hypertension, secondary hypertension, renovascular hypertension, chronic glomerulonephritis, erectile dysfunction, ventricular arrhythmia, diabetes, diabetes complications, nephropathy, retinopathy, angiogenesis, asthma bronchiale, chronic renal failure, cirrhosis of the liver, osteoporosis, restricted memory performance or a restricted ability to learn, or for the lowering of cardiovascular risk of postmenopausal women or after intake of contraceptives, the method comprising administering to the patient a pharmaceutically effective dose of a compound of the formula Ia,
- in which
- Het is a 5-membered to 10-membered, monocyclic or bicyclic, aromatic group which contains one or more identical or different heteroatom ring members chosen from N, NR4, O and S, and which can be substituted on ring carbon atoms by one or more identical or different substituents R5;
- X is chosen from a direct bond, CH2, O, CH2—O, O—CH2, S, NH and N((C1-C4)-alkyl), or X is absent and in this case the phenyl, naphthalenyl or heteroaryl group representing the group R3 is fused to the group Het, provided that X cannot be O, CH2—O, S, NH or N((C1-C4)-alkyl) if the group R3—X— is bonded to a ring nitrogen atom of the group Het;
- Ra, Rb, Rc and Rd are independently of each other chosen from hydrogen, fluorine and (C1-C4)-alkyl;
- R1 and R2 are independently of each other chosen from hydrogen, (C1-C10)-alkyl, (C3-C10)-alkenyl, (C3-C10)-alkynyl, (C3-C10)-cycloalkyl-CnH2n—, phenyl-CnH2n—, naphthalenyl-CnH2n— and heteroaryl-CnH2n—, wherein the groups (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-alkenyl and (C3-C10)-alkynyl can all be substituted by one or more identical or different substituents R6, and the groups CnH2n can all be substituted by one or more identical or different substituents chosen from fluorine and (C1-C4)-alkyl, and all phenyl, naphthalenyl and heteroaryl groups can independently of each other be substituted by one or more identical or different substituents R7, or R1 and R2, together with the nitrogen atom carrying them, form a 4-membered to 10-membered, monocyclic or bicyclic, saturated or unsaturated ring which, in addition to the ring nitrogen atom carrying R1 and R2, can contain one or two further heteroatom ring members chosen from N, NR9, O, S, SO and SO2 which can be identical or different, with the proviso that two ring members from the series O, S, SO and SO2 cannot be present in adjacent ring positions, wherein the ring formed by R1 and R2 together with the nitrogen atom carrying them can be substituted by one or more identical or different substituents R8;
- R3 is chosen from phenyl, naphthalenyl and heteroaryl which can all be substituted by one or more identical or different substituents chosen from halogen, (C1-C6)-alkyl, (C1-C6)-alkyloxy-(C1-C3)-alkyl-, OH, (C1-C6)-alkyloxy which can be substituted by one or more fluorine atoms, (C1-C3)-alkylenedioxy which can be substituted by one or more fluorine atoms, (C1-C6)-alkylmercapto, NH2, (C1-C6)-alkylamino, di((C1-C6)-alkyl)amino, ((C1-C6)-alkyl)-CONH—, ((C1-C6)-alkyl)-SO2NH—, di((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyloxy)carbonyl-, COOH, CONH2, CN, CF3, ((C1-C6)-alkyl)NHSO2—, di((C1-C6)-alkyl)NSO2—, H2NSO2— and (C1-C6)-alkyl-SO2—;
- R4 is chosen from hydrogen and (C1-C4)-alkyl;
- R5 is chosen from halogen, (C1-C6)-alkyl, (C1-C6)-alkyloxy-(C1-C3)-alkyl-, OH, (C1-C6)-alkyloxy which can be substituted by one or more fluorine atoms, (C1-C6)-alkylmercapto, NH2, (C1-C6)-alkylamino, di((C1-C6)-alkyl)amino, ((C1-C6)-alkyl)-CONH—, ((C1-C6)-alkyl)-SO2NH—, di((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyloxy)carbonyl-, COOH, CONH2, CN, CF3, H2NSO2—, ((C1-C6)-alkyl)NHSO2—, di((C1-C6)-alkyl)NSO2— and (C1-C6)-alkyl-SO2—;
- R6 is chosen from fluorine, OH, oxo, (C1-C6)-alkyloxy, (C1-C6)-alkylmercapto, di((C1-C6)-alkyl)amino, ((C1-C6)-alkyl)-CONH—, ((C1-C6)-alkyl)-SO2NH—, di((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyloxy)carbonyl-, CONH2, CN and CF3;
- R7 is chosen from halogen, (C1-C6)-alkyl, (C1-C6)-alkyloxy-(C1-C3)-alkyl-, OH, (C1-C6)-alkyloxy which can be substituted by one or more fluorine atoms, (C1-C3)-alkylenedioxy which can be substituted by one or more fluorine atoms, (C1-C6)-alkylmercapto, NH2, (C1-C6)-alkylamino, di((C1-C6)-alkyl)amino, ((C1-C6)-alkyl)-CONH—, ((C1-C6)-alkyl)-SO2NH—, di((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyloxy)carbonyl-, CONH2, CN, CF3, SF5, H2NSO2—, ((C1-C6)-alkyl)NHSO2—, di((C1-C6)-alkyl)NSO2— and (C1-C6)-alkyl-SO2—;
- R8 is chosen from halogen, (C1-C6)-alkyl, (C1-C6)-alkyloxy-(C1-C3)-alkyl-, OH, oxo, (C1-C6)-alkyloxy which can be substituted by one or more fluorine atoms, (C1-C3)-alkylenedioxy which can be substituted by one or more fluorine atoms, (C1-C6)-alkylmercapto, NH2, (C1-C6)-alkylamino, di((C1-C6)-alkyl)amino, ((C1-C6)-alkyl)-CONH—, ((C1-C6)-alkyl)-SO2NH—, di((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyloxy)carbonyl-, CONH2, CN, CF3, H2NSO2-, ((C1-C6)-alkyl)NHSO2—, di((C1-C6)-alkyl)NSO2— and (C1-C6)-alkyl-SO2—;
- R9 is chosen from hydrogen, (C1-C6)-alkyl, ((C1-C6)-alkyl)-CO— and phenyl-CO—, wherein the phenyl group can be substituted by one or more identical or different substituents chosen from halogen, (C1-C4)-alkyl, CF3 and (C1-C4)-alkyloxy;
- R10 is chosen from hydrogen and (C1-C4)-alkyl;
- heteroaryl is a 5-membered to 10-membered, monocyclic or bicyclic aromatic group which contains one or more identical or different heteroatom ring members chosen from N, NR10, O and S;
- and
- n is 0, 1, 2 or 3, where all numbers n are independent of each other and can be identical or different;
- in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof.