Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors.
نویسندگان
چکیده
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 μM 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.
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ورودعنوان ژورنال:
- Bioorganic & medicinal chemistry
دوره 20 17 شماره
صفحات -
تاریخ انتشار 2012