New dual inhibitors of EGFR and HER2 protein tyrosine kinases

A novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1-f][1,2,4]triazine nucleus is described. A general route toward their synthesis, which enables functionalization at multiple sites, has been developed. Biological evaluation in enzymatic and cell-based assays has identified a series of C-6 carbamates with potent biochemical and cellular activities.

Graphical abstractA novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1-f][1,2,4]triazine nucleus is described. Biological evaluation in enzymatic and cell-based assays has identified a series of C-6 carbamates with potent biochemical and cellular activities.Figure optionsDownload full-size imageDownload as PowerPoint slide