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 polyc...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2011-04, Vol.9 (8), p.2925-2937
Main Authors: Lin, Po-Tsung, Salunke, Deepak B, Chen, Li-Hsun, Sun, Chung-Ming
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:1477-0520
1477-0539
DOI:10.1039/c0ob01126f