Solid-phase analogue synthesis of caspase-3 inhibitors via palladium-catalyzed amination of 3-bromopyrazinones

Caspase-3 is a cysteinyl protease that mediates apoptotic cell death. Its inhibition may have an important impact on the treatment of several degenerative diseases. Here we report the synthesis of reversible inhibitors via a solid-support palladium-catalyzed amination of 3-bromopyrazinones and the discovery of a pan-caspase reversible inhibitor.