Soluble polymer supported divergent synthesis of tetracyclic benzene-fused pyrazino/diazepino indoles: an advanced synthetic approach to bioactive scaffolds

Org Biomol Chem. 2011 Apr 21;9(8):2925-37. doi: 10.1039/c0ob01126f. Epub 2011 Mar 3.

Abstract

The synthesis of indoline substituted nitrobenzene on a PEG support and its further elaboration to structurally diverse benzene-fused pyrazino/diazepino indoles is disclosed. A reagent based diversification approach coupled with Pictet-Spengler type condensation reactions furnished these fused polycyclic scaffolds. Microwave irradiation was used as a means of rate acceleration for soluble polymer-supported reactions. The efficiency of these fused heterocyclic molecules to inhibit the vascular endothelial growth factor receptor 3 (VEGFR-3) was examined in vitro using kinase receptor activation enzyme-linked immunosorbant assay (KIRA-ELISA). Based on the preliminary results obtained, a small set of potential drug candidates were identified as novel leads in this therapeutic area to be further explored as anti-metastatic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azepines / chemistry*
  • Benzene / chemical synthesis*
  • Benzene / pharmacology
  • Heterocyclic Compounds, 4 or More Rings / chemistry*
  • Indoles / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Polyethylene Glycols / chemistry*
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / pharmacology
  • Pyrazines / chemistry*
  • Solubility
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor Receptor-3 / antagonists & inhibitors

Substances

  • Azepines
  • Heterocyclic Compounds, 4 or More Rings
  • Indoles
  • Protein Kinase Inhibitors
  • Pyrazines
  • Polyethylene Glycols
  • Vascular Endothelial Growth Factor Receptor-3
  • Benzene