AXTEN, Jeffrey Michael,FAUCHER, Nicolas Eric,DAUGAN, Alain Claude-Marie
申请号:
IBIB2016/055505
公开号:
WO2017/046738A1
申请日:
2016.09.15
申请国别(地区):
WO
年份:
2017
代理人:
摘要:
The invention is directed to substituted triazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R4, R5, X, Y, Y1, and Z are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimers disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntingtons disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Picks disease, Neimann-Picks disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.Linvention concerne des dérivés de triazolidinone substitués. Linvention concerne spécifiquement des composés de formule I, dans laquelle R1, R2, R3, R4, R5, X, Y, Y1 et Z sont tels que définis dans la description. Les composés de linvention sont des inhibiteurs de PERK et peuvent être utiles dans le traitement du cancer, de