Discovery of indenopyrazoles as EGFR and VEGFR-2 tyrosine kinase inhibitors by in silico high-throughput screening

A series of indenopyrazoles 8 and 9 were designed and synthesized as EGFR tyrosine kinase inhibitors by in silico high-throughput screening. Compounds 8b and 8d showed significant inhibition of A431 cell growth (GI50 = 0.062 and 0.057 μM, respectively). Compounds 8b and 9a showed inhibitory activity toward both EGFR and VEGFR-2 (KDR) tyrosine kinases, whereas 8d inhibited VEGFR-2 tyrosine kinase, exclusively.

Graphical abstractIn silico high-throughput screening targeting to EGFR tyrosine kinase was carried out and indenopyrazoles were found to possess inhibitory activities toward EGFR and/or VEGFR tyrosine kinases.Figure optionsDownload full-size imageDownload as PowerPoint slide