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

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.
Dengyou Zhang 1,  Jing Ai,  Zhongjie Liang,  Chunpu Li,  Xia Peng,  Yinchun Ji,  Hualiang Jiang,  Meiyu Geng,  Cheng Luo,  Hong Liu
Affiliations

Affiliation

  • 1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, PR China.
PMID: 22863529 DOI: 10.1016/j.bmc.2012.07.007
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 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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