Novel azulene-based derivatives as potent multi-receptor tyrosine kinase inhibitors

A series of azulene-based derivatives were synthesized as potent inhibitors for receptor tyrosine kinases such as FMS-like tyrosine kinase 3 (FLT-3). Systematic side chain modification of prototype 1a was carried out through SAR studies. Analogue 22 was identified from this series and found to be one of the most potent FLT-3 inhibitors, with good pharmaceutical properties, superior efficacy, and tolerability in a tumor xenograft model.

Graphical abstractThe discovery of a novel series of multi-receptor tyrosine kinase inhibitor is disclosed.Figure optionsDownload full-size imageDownload as PowerPoint slide