IMIDAZOLIDINONE DERIVATIVES AS INHIBITORS OF PERK

The invention is directed to substituted imidazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I (I) wherein R1, R2, R3, R4, R5, R6, R7, X, Y1, Y2 and Z are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson 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. L'invention concerne des dérivés d'imidazolidinone substitués. L'invention concerne spécifiquement des composés de formule I (I), dans laquelle R1, R2, R3, R4, R5, R6, R7, X, Y1, Y2 sont tels que définis dans la description. Les composés de l'invention sont des inhibiteurs de PERK et peuvent être utiles dans le traitement du cancer, des syndromes précancéreux, tels que la maladie d'Alzheimer, de la douleur neuropathique, des lésions de la moelle épinière, d'une lésion cérébrale traumatique, de l'accident vasculaire cérébral ischémique, de l'accident vasculaire cérébral, de la maladie de Parkinson, du diabète, du syndrome métabolique, des troubles métaboliques, la maladie de Huntington, de la maladie de Creutzfeldt-Jakob, de l'insomnie familiale fatale, du syndrome de Gerstmann-Sträussler-Scheinker, et des