[EN] BENZENESULFONAMIDE DERIVATIVES AS TRAP1 MODULATORS AND USES THEREOF<br/>[FR] DÉRIVÉS DE BENZÈNESULFONAMIDE EN TANT QUE MODULATEURS TRAP1 ET UTILISATIONS ASSOCIÉES
申请人:AMATHUS THERAPEUTICS INC
公开号:WO2021188880A1
公开(公告)日:2021-09-23
The present disclosure provides compounds of Formula (I): and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, and prodrugs thereof. The provided compounds may be tumor necrosis factor ("TNF") receptor associated protein 1 ("TRAP1") modulators (e.g., TRAP1 activators). The provided compounds may also rescue the activity in PTEN-induced kinase 1 ("PINK1") loss of function contexts. The provided compounds may also improve mitochondrial health, function, quality, quantity, and/or activity, and/or reduce the production of reactive oxygen species. The provided compounds may also refold or solubilize aggregated or misfolded proteins such as α-synuclein. The present disclosure also provides pharmaceutical compositions comprising the provided compounds; kits comprising the provided compounds or pharmaceutical compositions; and methods of using the provided compounds and pharmaceutical compositions (e.g., for treating a disease in a subject in need thereof).
本公开提供了Formula (I)的化合物及其药用盐、溶剂化合物、水合物、多晶形态、共晶体、互变异构体、立体异构体、同位素标记化合物和其前药。所提供的化合物可能是肿瘤坏死因子("TNF")受体相关蛋白1("TRAP1")调节剂(例如,TRAP1激活剂)。所提供的化合物还可能在PTEN诱导激酶1("PINK1")功能丧失的情况下恢复活性。所提供的化合物还可能改善线粒体的健康、功能、质量、数量和/或活性,并/或减少活性氧自由基的产生。所提供的化合物还可能对α-突触核蛋白等聚集或错误折叠的蛋白进行重新折叠或溶解。本公开还提供了包含所提供化合物的药物组合物;包含所提供化合物或药物组合物的试剂盒;以及使用所提供化合物和药物组合物的方法(例如,用于治疗需要的受试者的疾病)。