Pyrrolo[3,4-c]quinoline-1,3-diones as potent caspase-3 inhibitors. Synthesis and SAR of 2-substituted 4-methyl-8-(morpholine-4-sulfonyl)-pyrrolo[3,4- c]quinoline-1,3-diones

Synthesis, biological evaluation and structure–activity relationships for a series of 2-substituted 4-methyl-8-(morpholine-4-sulfonyl)-1,3-dioxo-2,3-dihydro-1 H-pyrrolo[3,4- c]quinolines are described. These compounds represent a new chemotype of nonpeptide small molecule inhibitors of caspase-3. Among the studied compounds, several potent inhibitors with IC 50 in the range of 3–10 nM have been identified. The most active compound within this series, 7 {49} and 7 {58}, inhibited caspase-3 with IC 50 = 3 nM.