PRODRUG MODULATORS OF THE INTEGRATED STRESS PATHWAYProvided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases, disorders and conditions.A compound represented by Formula (I):or a pharmaceutically acceptable salt, co-crystal, solvate, hydrate, tautomer, ester, A'-oxidc or stereoisomer thereof, wherein:R1 is selected from the group consisting of -C(0)-Ci-4alkyl, -C(0)-0-Ci-4alkyl, -C(0)-N(Ra)-Ci-4alkyl, -C(0)-Ci-4alkylene-Ci-4alkoxy, -C(0)-Ci-4alkylene-0-Ci-4alkylene-Ci-4alkoxy, - methylene-0-P(0)(0H)2, -C(0)-Ci-5alkylene-0-P(0)(0H)2, -C(0)-0-Ci-5alkylene-0- P(0)(0H)2, -C(0)-N(Ra)-Ci-5alkylene-0-P(0)(0H)2, -C(0)-Ci-5alkylene-P(0)(0H)2, -C(0)-Ci- 5alkylene-phenylene-0-P(0)(0H)2, -C(0)-Ci-5alkylene-phenylene-(0-P(0)(0H)2)2, -C(0)-Ci- 5alkylene-phenylene-(0-P(0)(0H)2)(0-Ci-5alkylene-P(0)(0H)2), -methylene-0-C(0)Ci- 5alkylene-phenylene-0-P(0)(0H)2 or -methylene-0-C(0)Ci-5alkylene-phenylene-(0- P(0)(0H)2)2, -C(0)-0-Ci-5alkylene-0-C(0)Ci-5alkylene-phenylene-0-P(0)(0H)2, -C(0)-N(Ra)- heteroarylene-Ci-2alkylene-0-P(0)(OH)2, -P(0)(0H)2, -SO3H, -S02NRaRb, -C(0)-heteroaryl, - C(0)-Ci-5alkylene-0-Ci-5alkylene-phenyl and methylene-Ci-salkoxide;wherein -C(0)-Ci-4alkyl is substituted by one or two substituents each independently selected from the group consisting of-NRaRb and -CO2H; and wherein -C(0)-0-Ci-4alkyl, - C(0)-N(Ra)-Ci-4alkyl, -C(0)-Ci-4alkylene-Ci-4alkoxy, -C(0)-Ci-4alkylene-0-Ci-4alkylene-Ci- 4alkoxy, methylene-0-P(0)(0H)2, -C(0)-Ci-5alkylene-0-P(0)(0H)2, -C(0)-0-Ci-5alkylene-0- P(0)(0H)2, -C(0)-N(Ra)-Ci-5alkylene-0-P(0)(0H)2, -C(0)-Ci-5alkylene-P(0)(0H)2, -C(0)-Ci- 5alkylene-phenylene-0-P(0)(0H)2, -C(0)-Ci-5alkylene-phenylene-(0-P(0)(0H)2)2, -C(0)-Ci- 5alkylene-phenylene-(0-P(0)(0H)2)(0-Ci-5alkylene-P(0)(0H)2), -methylene-0-C(0)Ci- 5alkylene-phenylene-0-P(0)(0H)2 or -methylene-0-C(0)Ci-5alkylene-phenylene-(0- P(0)(0H)2)2, -C(0)-0-Ci-5alkylene-0-C(0)Ci-5alkylene-phenylene-0-P(0)(0H)2, -C(O)- heteroaryl, -C(0)-Ci-5alkylene-0-Ci-5alkylene-phenyl and -C(0)-N(Ra)-heteroarylene-Ci- 2alkylene-0-P(0)(0H)2 may optionally be substituted by one, two, three or four substituents each independently selected from the group consisting of halogen, -CO2H, -NRaRb and Ci-2alkyl (optionally substituted by one, two or three fluorines) and aryl; andRa and Rb are independently selected, for each occurrence, from the group consisting of hydrogen and C 1-3 alkyl. 
통합된 스트레스 경로의 전구약물 조절인자통합된 스트레스 반응 (ISR) 조절 및 관련 질환; 장애 및 병태 치료에 유용한 화합물, 조성물, 및 방법이 본원에 제공된다.화학식 (I)에 의해 나타나는 화합물: (I); 또는 이의 약학적으로 허용 가능한 염, 공결정, 용매화물, 수화물, 호변이성질체, 에스테르, N-옥사이드 또는 입체이성질체, 여기서:R1은 -C(O)-C1-4알킬, -C(O)-O-C1-4알킬, -C(O)-N(Ra)-C1-4알킬, -C(O)-C1-4알킬렌-C1-4알콕시, -C(O)-C1-4알킬렌-O-C1-4알킬렌-C1-4알콕시, -메틸렌-O-P(O)(OH)2, -C(O)-C1-5알킬렌-O-P(O)(OH)2, -C(O)-O-C1-5알킬렌-O-P(O)(OH)2, -C(O)-N(Ra)-C1-5알킬렌-O-P(O)(OH)2, -C(O)-C1-5알킬렌-P(O)(OH)2, -C(O)-C1-5알킬렌-페닐렌-O-P(O)(OH)2, -C(O)-C1-5알킬렌-페닐렌-(O-P(O)(OH)2)2, -C(O)-C1-5알킬렌-페닐렌-(O-P(O)(OH)2)(O-C1-5알킬렌-P(O)(OH)2), -메틸렌-O-C(O)C1-5알킬렌-페닐렌-O-P(O)(OH)2 또는 -메틸렌-O-C(O)C1-5알킬렌-페닐렌-(O-P(O)(OH)2)2, -C(O)-O-C1-5알킬렌-O-C(O)C1-5알킬렌-페닐렌-O-P(O)(OH)2, -C(O)-N(Ra)-헤테로아릴렌-C1-2알킬렌-O-P(O)(OH)2, -P(O)(OH)2, -SO3H, -SO2NRaRb, -C(O)-헤테로아릴, -C(O)-C1-5알킬렌-O-C1-5알킬렌-페닐 및 메틸렌-C1-5알콕사이드로 이루어진 군으로부터 선택되고; 여기서 -C(O)-C1-4알킬은 -NRaRb 및 -CO2H로 이루어진 군으로부터 각각 독립적으로 선택된 하나 또는 둘의 치환기에 의해 치환되고; 여기서 -C(O)-O-C1-4알킬, -C(O)-N(Ra)-C1-4알킬, -C(O)-C1-4알킬렌-C1-4알콕시, -C(O)-C1-4알킬렌-O-C1-4알킬렌-C1-4알콕시, 메틸렌-O-P(O)(OH)2, -C(O)-C1-5알킬렌-O-P(O)(OH)2, -C(O)-O-C1-5알킬렌-O-P(O)(OH)2, -C(O)-N(Ra)-C1-5알킬렌-O-P(O)(OH)2, -C(O)-C1-5알킬렌-P(O)(OH)2, -C(O)-C1-5알킬렌-페닐렌-O-P(O)(OH)2, -C(O)-C1-5알킬렌-페닐렌-(O-P(O)(OH)2)2, -C(O)-C1-5알킬렌-페닐렌-(O-P(O)(OH)2)(O-C1-5알킬렌-P(O)(OH)2), -메틸렌-O-C(O)C1-5알킬렌-페닐렌-O-P(O)(OH)2 또는 -메틸렌-O-C(O)C1-5알킬렌-페닐렌-(O-P(O)(OH)2)2, -C(O)-O-C1-5알킬렌-O-C(O)C1-5알킬렌-페닐렌-O-P(O)(OH)2, -C(O)-헤테로아릴, -C(O)-C1-5알킬렌-O-C1-5알킬렌-페닐 및 -C(O)-N(Ra)-헤테로아릴렌-C1-2알킬렌-O-P(O)(OH)2는 할로겐, -CO2H, -NRaRb 및 C1-2알킬 (하나, 둘 또는 셋의 플루오린에 의해 선택적으로 치환됨) 및 아릴로 이루어진 군으로부터 각각 독립적으로 선택된 하나, 둘, 셋 또는 넷의 치환기에 의해 선택적으로 치환될 수 있고; Ra 및 Rb는, 각 경우에, 수소 및 C1-3알킬로 이루어진 군으로부터 독립적으로 선택된다.