4-AMINO-2-(1H-PYRAZOLO[3,4-B]PYRIDIN-3-YL)-6-OXO-6,7-DIHYDRO-5H- PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES AND THE RESPECTIVE (1H-INDAZOL-3-YL) DERIVATIVES AS CGMP MODULATORS FOR TREATING CARDIOVASCULAR DISEASES

The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1, R2, R4, Ra, and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guan...

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Hauptverfasser: Guoqing LI, Yi- Heng CHEN, Jianmin FU, Yong ZHANG, John STELMACH, Cameron J. SMITH, Raphelle BERGER, Rui ZHANG, Shouwu MIAO, Hong LI, Alan WHITEHEAD, Gang JI, Falong JIANG, Joie GARFUNKLE, Subharekha RAGHAVAN
Format: Patent
Sprache:eng ; spa
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Zusammenfassung:The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1, R2, R4, Ra, and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate ("cGMP"), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance, such as cardiovascular disease, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, heart failure, pulmonary hypertension (WHO groups I, II, III, IV), angina pectoris, thrombosis, restenosis, myocardial infarction, stroke, cardiac insufficiency, fibrosis, pulmonary hypertonia, erectile dysfunction, asthma, acute respiratory distress syndrome (ARDS), chronic kidney disease, cystic fibrosis, sickle cell anemia, scleroderma, Raynaud's Syndrome, diabetes, diabetic retinopathy, cirrhosis of the liver, chronic obstructive pulmonary disease (COPD), acute lung injury, pulmonary fibrosis or interstitial lung disease. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to the compounds or their pharmaceutically acceptable salts for use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose. La invención proporciona compuestos de la fórmula (I) (ver Fórmula) o una sal farmacéuticamente aceptable de los mismos, en la que X, Y, Z, R1, R2, R4, Ra y los subíndices m, p y q son tal como se describen en el presente documento. Los compuestos o sus sales farmacéuticamente aceptables pueden modular la producción corporal de guanosín monofosfato cíclico ("GMPc") y son generalmente adecuados para el tratamiento y prevención de enfermedades que están asociadas con un equilibrio de GMPc perturbado, tales como enfermedad cardiovascular, disfunción endotelial, disfunción diastólica, aterosclerosis, hipertensión, insuficiencia cardiaca, hipertensión pulmonar (grupos I, II, III, IV de la OMS), angina de pecho, trombosis, restenosis, infarto de miocardio, apoplejía, insuficiencia cardiaca, fibrosis, hipertonía pulmonar, disfunción eréctil, asma, síndrome de dificultad respiratoria aguda (ARDS), enfermedad renal crónica, fibrosis quística, anemia de células falciformes, esclerodermia, síndrome de Raynaud, diabetes, retinopatía diabética, cirrosis h