[EN] BICYCLO[1.1.1]PENTANE INHIBITORS OF DUAL LEUCINE ZIPPER (DLK) KINASE FOR THE TREATMENT OF DISEASE<br/>[FR] INHIBITEURS BICYCLO[1.1.1]PENTANE DE LA DOUBLE FERMETURE À GLISSIÈRE DE LEUCINE KINASE (DLK) DESTINÉS AU TRAITEMENT DE MALADIE
申请人:UNIV TEXAS
公开号:WO2021081074A1
公开(公告)日:2021-04-29
Disclosed herein are compounds which inhibit the kinase activity of dual leucine zipper (DLK) kinase (MAP3K12), pharmaceutical compositions, and methods of treatment of DLK-mediated diseases, such as neurological diseases that result from traumatic injury to central nervous system and peripheral nervous system neurons (e.g. stroke, traumatic brain injury, spinal cord injury), or that result from a chronic neurodegenerative condition (e.g. Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinocerebellar ataxia, progressive supranuclear palsy, Lewy body disease, Kennedy's disease, and other related conditions), from neuropathies resulting from neurological damage (chemotherapy-induced peripheral neuropathy, diabetic neuropathy, and related conditions) and from cognitive disorders caused by pharmacological intervention (e.g. chemotherapy induced cognitive disorder, also known as chemobrain).
本文披露了一种抑制双亮氨酸拉链(DLK)激酶(MAP3K12)激酶活性的化合物,以及用于治疗DLK介导的疾病的药物组合物和方法,例如由中枢神经系统和外周神经系统神经元的创伤性损伤导致的神经疾病(例如中风、创伤性脑损伤、脊髓损伤),或由慢性神经退行性疾病导致的疾病(例如阿尔茨海默病、额颞叶痴呆、帕金森病、亨廷顿病、肌萎缩性侧索硬化、脊髓小脑共济失调、进行性上视神经麻痹、Lewy小体病、肯尼迪病和其他相关疾病),以及由神经损伤引起的神经病(化疗引起的周围神经病、糖尿病性神经病和相关疾病)和由药物干预引起的认知障碍(例如化疗引起的认知障碍,也称为化疗脑)。