Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors

A series of acylurea analogs derived from pyrrolopyridine and aminopyridine scaffolds were identified as potent inhibitors of Met kinase activity. The SAR at various positions of the two kinase scaffolds was investigated. These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model.

Graphical abstractA series of acylurea analogs derived from pyrrolopyridine and aminopyridine scaffolds were identified as potent inhibitors of Met kinase activity. The SAR studies led to the discovery of compounds 3b and 20b, which demonstrated significant antitumor activity in a human gastric carcinoma xenograft model.Figure optionsDownload full-size imageDownload as PowerPoint slide