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

Eur J Med Chem. 2005 Dec;40(12):1377-83. doi: 10.1016/j.ejmech.2005.07.011. Epub 2005 Sep 15.

Abstract

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-1H-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 IC50 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 IC50=3 nM.

MeSH terms

  • Caspase 3
  • Caspase Inhibitors*
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Molecular Structure
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Caspase Inhibitors
  • Enzyme Inhibitors
  • Quinolones
  • Caspase 3