Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors.

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Zhang D, Ai J, Liang Z, Li C, Peng X, Ji Y, Jiang H, Geng M, Luo C, Liu H

Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors.

Bioorg Med Chem. 2012 Sep 1;20(17):5169-80. doi: 10.1016/j.bmc.2012.07.007. Epub 2012 Jul 16.

PubMed ID

22863529 [ View in PubMed

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Abstract

A series of 2-aminopyridine-3-carboxamide derivatives against c-Met were designed and synthesized by employing bioisosteric replacement of heterocyclic moieties with the amide bond. The structure-activity relationship (SAR) at various positions of the scaffold was explored. In this study, a promising compound (S)-24o with a c-Met IC(50) of 0.022 muM was identified. The compound exhibited dose-dependent inhibition of the phosphorylation of c-Met as well as downstream signaling in EBC-1 cells. Furthermore, the interactive binding model of (S)-24o with c-Met was elucidated by virtue of a molecular modeling study.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Crizotinib	Hepatocyte growth factor receptor	IC 50 (nM)	1.6	N/A	N/A	Details