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

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Cai ZW, Wei D, Schroeder GM, Cornelius LA, Kim K, Chen XT, Schmidt RJ, Williams DK, Tokarski JS, An Y, Sack JS, Manne V, Kamath A, Zhang Y, Marathe P, Hunt JT, Lombardo LJ, Fargnoli J, Borzilleri RM

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

Bioorg Med Chem Lett. 2008 Jun 1;18(11):3224-9. doi: 10.1016/j.bmcl.2008.04.047. Epub 2008 Apr 25.

PubMed ID

18479916 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
2-(4-fluorophenyl)-N-{[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]carbamoyl}acetamide	Hepatocyte growth factor receptor	IC 50 (nM)	110	N/A	N/A	Details
N-({4-[(2-aminopyridin-4-yl)oxy]-3-fluorophenyl}carbamoyl)-2-(4-fluorophenyl)acetamide	Hepatocyte growth factor receptor	IC 50 (nM)	35	N/A	N/A	Details