Synthesis and biological evaluation of new dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraones, substituted with various saturated and unsaturated side chains via palladium catalyzed cross-coupling reactions

Bioorg Med Chem. 2006 Jun 1;14(11):3825-34. doi: 10.1016/j.bmc.2006.01.030. Epub 2006 Feb 3.

Abstract

The syntheses of a series of dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraones, substituted in 10-position with saturated and unsaturated side chains, via palladium catalyzed cross-coupling reactions, are described. These compounds can be considered as granulatimide bis-imide analogues. Their inhibitory activity toward Chk1 kinase and their antiproliferative activities in vitro in four tumor cell lines are reported.

MeSH terms

  • Animals
  • Carbazoles / chemical synthesis*
  • Carbazoles / pharmacology*
  • Catalysis
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Checkpoint Kinase 1
  • Cyclization
  • Drug Screening Assays, Antitumor
  • Humans
  • In Vitro Techniques
  • Molecular Structure
  • Palladium / chemistry*
  • Protein Kinases / drug effects
  • Pyrroles / chemical synthesis*
  • Pyrroles / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Carbazoles
  • Pyrroles
  • dipyrrolo(3,4-a:3,4-c)carbazole-1,3,4,6-tetraone
  • Palladium
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1