Giovanni APPENDINO,María Luz BELLIDO CABELLO DE ALBA,Eduardo MUÑOZ BLANCO,Alberto MINASSI
申请号：
MX2019005448
公开号：
MX2019005448A
申请日:
2018.05.24
申请国别(地区):
MX
年份:
2019
代理人:
摘要：
Triterpenoid derivatives and compositions comprising said triterpenoids derivatives of Formula (I) are described, wherein R=-C(O)NHOH. Said triterpenoids and compositions show capacity to bind PHD2, stabilize HIF-1a and HIF-2a proteins, activate the HIF pathway in different cell types, induce angiogenesis in human endothelial vascular cell, show neuroprotective activity in vitro and in vivo, antidiabetic activity and reduce the levels of lipids in vivo, and increase the plasma levels of Erythropoietin in vivo. The triterpenoid derivatives described act also in a selective manner and do not induce Nrf2 activation, NF-?B inhibition, STAT3 inhibition, and TGR5 activation, which are known activities of the natural triterpenoid precursors. Said triterpenoid derivatives are useful in the treatment of conditions and diseases which are responsive to HIF activation such as stroke, cerebral palsy, traumatic injuries and neurodegenerative diseases； and also IBD, myocardial ischaemi-reperfusion injury, acute lung injury, diabetic and chronic wounds, organ transplantation, acute kidney injury or arterial diseases.Se describen derivados triterpenoides y composiciones que comprenden dichos derivados triterpenoides de Fórmula (I), donde R=-C(O)NHOH. Dichos triterpenoides y composiciones muestran capacidad de unión a PHD2, estabilizan las proteínas HIF-1a y HIF-2a, activan la ruta HIF en diferentes tipos celulares, inducen angiogénesis en células vasculares endoteliales humanas, muestran actividad neuroprotectora in vitro e in vivo, actividad antidiabética y reducen los niveles de lípidos in vivo, y aumentan los niveles en plasma de eritropoyetina in vivo. Los derivados triterpenoides descritos actúan también de forma selectiva y no inducen activación de Nrf2, inhibición de NF-?B, inhibición de STAT3, y activación de TGR5, que son actividades conocidas de precursores triterpenoides naturales. Dichos derivados triterpenoides son útiles en el tratamiento de afecciones y enfermedades q
