4-amino-2- (1h-pyrazolo [3,4-b] pyridin-3-yl) -6-oxo-6,7-dihydro-5h-pyrrolo [2,3-d] pyrimidine derivatives and (1h-indazol-3-yl) derivatives thereof as cgmp modulators for the treatment of cardiovascular disease
ALAN WHITEHEAD,CAMERON J. SMITH,FALONG JIANG,GANG JI,GUOQING LI,HONG LI,JIANMIN FU,JOHN STELMACH,JOIE GARFUNKLE,RAPHELLE BERGER,RUI ZHANG,SHOUWU MIAO,SUBHAREKHA RAGHAVAN,YI-HENG CHEN,YONG ZHANG
申请号：
BR112018012579
公开号：
BR112018012579A2
申请日:
2016.12.20
申请国别(地区):
BR
年份:
2018
代理人:
摘要：
The present invention provides compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein x, y, z, r 1, r 2, r 4, ra, and indices m, p, and q are as described herein. The compounds or pharmaceutically acceptable salts thereof may modulate body production of cyclic guanosine monophosphate ("cgmp") and are generally suitable for the therapy and prophylaxis of diseases that are associated with a disturbed cgmp balance such as cardiovascular disease, endothelial dysfunction, diastolic, atherosclerosis, hypertension, heart failure, pulmonary hypertension (who groups i, ii, iii, iv), angina pectoris, thrombosis, restenosis, myocardial infarction, stroke, heart failure, fibrosis, pulmonary hypertonia, erectile dysfunction, asthma , acute respiratory distress syndrome (ards), chronic kidney disease, cystic fibrosis, sickle cell anemia, scleroderma, raynaud 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 comprising compounds of formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to compounds or pharmaceutically acceptable salts thereof for use in therapy and prophylaxis of the above mentioned diseases and for pharmaceutical preparations therefor.a presente invenção fornece compostos da fórmula (i) ou sais farmaceuticamente aceitáveis dos mesmos, em que x, y, z, r1, r2, r4, ra, e os índices m, p, e q são como descrito aqui. os compostos ou seus sais farmaceuticamente aceitáveis podem modular a produção corporal de monofosfato cíclico de guanosina ("cgmp") e são geralmente adequados para a terapia e profilaxia de doenças que são associadas com um equilíbrio de cgmp perturbado como doença cardiovascular, disfunção endotelial, disfunção diastólica, aterosclerose, hipertensão, falência cardíaca, hipertensão pulmonar (who grupos i, ii, iii, iv)
