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 IC₅₀ 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.

中文翻译：

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发现新型的2-氨基吡啶-3-羧酰胺作为c-Met激酶抑制剂

通过利用酰胺键对杂环部分进行生物等位取代，设计和合成了一系列针对c-Met的2-氨基吡啶-3-羧酰胺衍生物。探索了支架在不同位置的构效关系（SAR）。在这项研究中，确定了一种有前途的化合物（S）-24o，其c-Met IC ₅₀为0.022μM。该化合物在EBC-1细胞中表现出剂量依赖性的c-Met磷酸化抑制作用以及下游信号传导。此外，借助于分子建模研究阐明了（S）-24o与c-Met的相互作用结合模型。