SIDRAUSKI, Carmela,PLIUSHCHEV, Marina,FROST, Jennifer M.,BLACK, Lawrence A.,XU, Xiangdong,SWEIS, Ramzi Farath,SHI, Lei,ZHANG, Qinwei I.,TONG, Yunsong,HUTCHINS, Charles W.,CHUNG, Seungwon,DART, Michael
申请号：
PE2018002316
公开号：
PE20190348A1
申请日:
2017.05.05
申请国别(地区):
PE
年份:
2019
代理人:
摘要：
Referred to compounds of Formula I or their pharmaceutically acceptable salts, solvates, hydrates, tautomers or stereoisomers, which are modulators of the integrated stress pathway (ISR). These compounds of formula (I) are characterized in that: D is a cycloalkyl, bridged monocyclic, bridged monocyclic heterocycle or cubanyl, among others； L1 and L2 are independently, C1-C6 alkylene, C2-C6 alkenylene, among others； R1 and R2 are independently, H, C1-C6 alkyl, C1-C6 alkoxy, among others； A and W are independently phenyl, or 5-6 membered heteroaryl；T is 0 or 1. The most popular compounds include: 2 - (4-chloro-3-fluoronoxi) - N - (2S) - 4 - [2 - (4-chlorophenol) acetyl] - 2-hydroxypropene [2.2.2] octan-1-il； 2 - (3,4-dichloro-3-fluoronoxi) - N - {3 - [2 - (pyridine-2-il) ethyl] bicycle [1.1] pentachlorophenylethyl； and others. It also refers to the constitution, production methods and the diseases and diseases related to neurodegenerative diseases, leukaemia, cancer, etc.Referido a compuestos de Formula I o sus sales, solvatos, hidratos, tautomeros o estereoisomeros farmaceuticamente aceptables, los cuales son moduladores de la via de estres integrada (ISR). Estos compuestos de formula (I) se caracterizan porque: D es un cicloalquilo, monociclico en puente, heterociclo monociclico en puente o cubanilo, entre otros； L1 y L2 son independientemente, alquileno C1-C6, alquenileno C2-C6, entre otros； R1 y R2 son independientemente, H, alquilo C1-C6, alcoxi C1-C6, entre otros； A y W son independientemente fenilo, o heteroarilo de 5-6 miembros； t es 0 o 1. Entre los compuestos preferidos tenemos: 2-(4-cloro-3-fluorofenoxi)-N-{(2S)-4-[2-(4-clorofenoxi)acetamido]-2-hidroxibiciclo[2.2.2]octan-1-il}acetamida； 2-(3,4-dicloro-3-fluorofenoxi)-N-{3-[2-(piridin-2-il)acetamido]biciclo[1.1.1]pentan-1-il}acetamida； entre otros. Tambien se refiere a composiciones, metodos de produccion y su uso para modular la ISR y para tratar enfermedades, trastornos y afecciones relacionados como enfer
