公开(公告)号：EP3350185A1

公开(公告)日：2018-07-25

申请号：EP16770800.7

申请日：2016-09-15

申请人： GlaxoSmithKline Intellectual Property (No. 2) Limited

发明人： AXTEN, Jeffrey Michael ,  FAUCHER, Nicolas Eric ,  DAUGAN, Alain Claude-Marie ,  KETHIRI, Raghava Reddy ,  KRISTAM, Rajendra ,  VENKATESHAPPA, Chandregowda

IPC分类号： C07D487/04 ,  A61K31/519 ,  C07D495/04 ,  A61P35/00 ,  A61P25/00 ,  A61P3/00

CPC分类号： C07D487/04 ,  A61K31/519 ,  A61K45/06 ,  C07D495/04

摘要： The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases/injuries associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson's disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's 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, Pick's disease, Neimann-Pick's 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.