Macrocycle thioester prodrugs as inhibitors of histone deacetylases

摘要

PRODrugs of macrocyclic inhibitors of histone deacetylases, their synthesis and methods of their use. In an exemplary embodiment, (R)-S-((E)-4-((7S,10S)-7-isopropyl-4,4-dimethyl-2,5,8,12-tetraoxo- 9-oxa-16-thia-3,6,13,18-tetraazabicyclo[13.2.1]octadeca-1(17),15(18)-dien-10-yl)but-3-ene- 1-yl) 2-amino-3-methylbutanethioate or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein administration of the compound results in a disease mediated by an HDAC enzyme. Provide a method for treating. [Selection diagram] Figure 2