Synthesis and Evaluation of Indole Aspartyl Ketones as Novel Caspase-3 Inhibitors

Abstract

Synthesis, biological evaluation and structure-activity relationships for a series of novel nonpeptide small molecule inhibitors of caspase-3 are described. Among the synthesized compounds, 2,3,5,6-tetrafluorophenoxymethyl ketone derivatives of indole-N-acetamides have been identified as potent inhibitors of caspase-3. The most active compound within this series (9a) inhibited caspase-3 with an IC₅₀ = 0.64 μM.