کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1359924 981420 2012 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors
چکیده انگلیسی

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.

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 SAR exploration led to the identification of a potent compound (S)-24o with a c-Met IC50 of 0.022 μM. This compound exhibited dose-dependent inhibition of the phosphorylation of c-Met as well as c-Met downstream signaling in EBC-1 cells. The interactive binding model of (S)-24o was elucidated using AutoDock4.2.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 17, 1 September 2012, Pages 5169–5180
نویسندگان
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