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Synthesis and biological evaluation of p38α kinase-targeting dialkynylimidazoles
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Nov2009, Vol. 19 Issue 22, p6293-6297. 5p. - Publication Year :
- 2009
-
Abstract
- Abstract: 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 =200nM) and selective inhibitor of p38α. Moreover, compound 14 covalently modifies p38α as determined by ESI-MS after 12h 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 19
- Issue :
- 22
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 44828021
- Full Text :
- https://doi.org/10.1016/j.bmcl.2009.09.094