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

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.