A method for treating a cardiovascular disease, 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, endothel 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 lowering cardiovascular risk of postmenopausal women or after intake of contraceptives, in a patient in need thereof, comprising administering to the patient an effective amount of a compound of formula Ia,
- wherein:
- A is —CH═CH—CH2—, —C≡C—CH2—, a group of formula II, or a group of the formula III,
- and is optionally substituted by one or more identical or different substituents R4;
- Het is a 5-membered to 10-membered, monocyclic or bicyclic, aromatic group which contains one or more identical or different hetero ring members selected from the group consisting of N, NR13, O and S, and is optionally substituted by one or more identical or different substituents R5;
- X is a direct bond, CH2, O, S, NH or 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;
- R1 and R2 are independently of each other (C1-C10)-alkyl, (C3-C10)-alkenyl, (C3-C10)-alkynyl, (C3-C10)-cycloalkyl-CnH2n—, phenyl-CnH2n—, naphthalenyl-CnH2n— and heteroaryl-CnH2n—, and R2 can in addition be hydrogen, wherein the groups (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-alkenyl and (C3-C10)-alkynyl are independently of each other optionally substituted by one or more identical or different substituents R6, and the group CnH2n is optionally substituted by one or more identical or different substituents selected from the group consisting of fluorine and (C1-C4)-alkyl, and all phenyl, naphthalenyl and heteroaryl groups are independently of each other optionally substituted by one or more identical or different substituents R7, or R1 and R2, together with the N—CO group to which they are attached, form a 4-membered to 10-membered, monocyclic or bicyclic, saturated or unsaturated ring which, in addition to the ring nitrogen atom being part of the N—CO group, optionally contain one or two additional hetero ring members selected from the group consisting of N, NR12, O, S, SO and SO2 which can be identical or different, provided that two ring members selected from O, S, SO and SO2 cannot be present in adjacent ring positions, wherein the 4-membered to 10-membered ring is optionally substituted by one or more identical or different substituents R8;
- R3 is phenyl, naphthalenyl or heteroaryl, each of which is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, (C1-C6)-alkyloxy-(C1-C6)-alkyl-, OH, (C1-C6)-alkyloxy, (C1-C3)-alkylenedioxy, (C1-C6)-alkylmercapto, NH2, (C1-C6)-alkylamino, di((C1-C6)-alkyl)amino, ((C1-C6)-alkyl)-CONH—, 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—, wherein the substituents (C1-C6)-alkyloxy and (C1-C3)-alkylenedioxy are each independently optionally substituted by one or more fluorine atoms;
- R4 is (C1-C6)-alkyl, halogen or oxo;
- R5 is halogen, (C1-C6)-alkyl, phenyl-CnH2n—, (C1-C6)-alkyloxy-(C1-C3)-alkyl-, OH, (C1-C6)-alkyloxy, (C1-C6)-alkylmercapto, NH2, (C1-C6)-alkylamino, di((C1-C6)-alkyl)amino, ((C1-C6)-alkyl)-CONH—, 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—, wherein the substituent (C1-C6)-alkyloxy is optionally substituted by one or more fluorine atoms, and the phenyl group is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C4)-alkyl, CF3 and (C1-C4)-alkyloxy;
- R6 is fluorine, OH, oxo, (C1-C6)-alkyloxy, (C1-C6)-alkylmercapto, di((C1-C6)-alkyl)amino, ((C1-C6)-alkyl)-CONH—, di((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyloxy)carbonyl-, COOH, CONH2, CN or CF3;
- R7 is halogen, (C1-C6)-alkyl, (C1-C6)-alkyloxy-(C1-C3)-alkyl-, OH, (C1-C6)-alkyloxy, (C1-C3)-alkylenedioxy, (C1-C6)-alkylmercapto, NH2, (C1-C6)-alkylamino, di((C1-C6)-alkyl)amino, ((C1-C6)-alkyl)-CONH—, di((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyloxy)carbonyl-, COOH, CONH2, CN, CF3, SF5, H2NSO2—, ((C1-C6)-alkyl)NHSO2—, di((C1-C6)-alkyl)NSO2— and (C1-C6)-alkyl-SO2—, wherein the substituents (C1-C6)-alkyloxy and (C1-C3)-alkylenedioxy are each independently optionally substituted by one or more fluorine atoms;
- R8 is halogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl-CnH2n—, phenyl-CnH2n—, heteroaryl-CnH2n—, (C1-C6)-alkyloxy-(C1-C3)-alkyl-, OH, oxo, (C1-C6)-alkyloxy, (C1-C3)-alkylenedioxy, (C1-C6)-alkylmercapto, NH2, (C1-C6)-alkylamino, di((C1-C6)-alkyl)amino, ((C1-C6)-alkyl)-CONH—, di((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyl)aminocarbonyl-, ((C1-C6)-alkyloxy)carbonyl-, COOH, CONH2, CN, CF3, SF5, H2NSO2— or (C1-C6)-alkyl-SO2—, wherein the substituents (C1-C6)-alkyloxy and (C1-C3)-alkylenedioxy are each independently optionally substituted by one or more fluorine atoms, and all phenyl groups and heteroaryl groups are independently of each other optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C4)-alkyl, CF3 and (C1-C4)-alkyloxy;
- R12 is hydrogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl-CnH2n—, phenyl-CnH2n—, heteroaryl-CnH2n—, ((C1-C6)-alkyl)-CO—, (C3-C7)-cycloalkyl-CnH2n—CO—, phenyl-CnH2n—CO—, heteroaryl-CnH2n—CO—, ((C1-C6)-alkyl)-O—CO— or phenyl-CnH2n—O—CO—, wherein all phenyl groups and heteroaryl groups are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C4)-alkyl, CF3 and (C1-C4)-alkyloxy;
- R13 is hydrogen, (C1-C4)-alkyl or phenyl-CnH2n—, wherein the phenyl group is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C4)-alkyl, CF3 and (C1-C4)-alkyloxy;
- heteroaryl is a 5-membered to 10-membered, monocyclic or bicyclic aromatic group which contains one or more identical or different hetero ring members selected from the group consisting of N, NR13, O and S;
- n is 0, 1, 2 or 3;
- q is 1, 2, 3, 4 or 5;
- r is 0 or 1;
- and
- s is 1, 2, 3 or 4;
- or its stereoisomeric form or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof.