کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1372704 | 981879 | 2009 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis and biological evaluation of p38α kinase-targeting dialkynylimidazoles Synthesis and biological evaluation of p38α kinase-targeting dialkynylimidazoles](/preview/png/1372704.png)
Based on the mild, thermal rearrangement of 1,2-dialkynylimidazoles to reactive carbene or diradical intermediates, a series of 1,2-dialkynylimidazoles were designed as potential irreversible p38 MAP kinase α-isoform (p38α) inhibitors. The synthesis of these dialkynylimidazoles and their kinase inhibition activity is reported. The 1-ethynyl-substituted dialkynylimidazole 14 is a potent (IC50 = 200 nM) and selective inhibitor of p38α. Moreover, compound 14 covalently modifies p38α as determined by ESI-MS after 12 h incubation at 37 °C. The unique kinase inhibition, covalent kinase adduct formation, and minimal CYP450 2D6 inhibition by compound 14 demonstrate that dialkynylimidazoles are a new, promising class of p38α inhibitors.
The dialkynylimidazole 14 is a potent (IC50 = 200 nM) and selective inhibitor that covalently modifies p38α.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 22, 15 November 2009, Pages 6293–6297