Center for Cell Signaling & Drug Discovery Research, College of Pharmacy and Division of Life & Pharmaceutical Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Republic of Korea.
Bioorg Med Chem Lett. 2013 Feb 15;23(4):1083-6. doi: 10.1016/j.bmcl.2012.12.008. Epub 2012 Dec 20.
A series of 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles has been synthesized and evaluated for their ALK5 inhibitory activity. The 1-(6-methylpyridin-2-yl)-1,2,3-triazoles were assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition. Following this, quinoxaline was introduced through Pd-catalyzed direct arylation. The synthesized 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles revealed significant selectivity differences with respect to p38α MAP kinase. In particular, 12k showed 80.8% ALK5 inhibitory activity at a concentration of 10 μM and IC(50) value of 4.69 μM, but did not show p38α MAP kinase inhibitory activity (-1.94% inhibition at a concentration of 10 μM).
已经合成了一系列 1-(6-甲基吡啶-2-基)-5-(喹喔啉-6-基)-1,2,3-三唑，并评估了它们对 ALK5 的抑制活性。1-(6-甲基吡啶-2-基)-1,2,3-三唑是通过 Cu(I)催化的叠氮-炔烃 1,3-偶极环加成反应组装的。随后，通过 Pd 催化的直接芳基化反应引入喹喔啉。所合成的 1-(6-甲基吡啶-2-基)-5-(喹喔啉-6-基)-1,2,3-三唑对 p38α MAP 激酶表现出显著的选择性差异。特别是化合物 12k 在 10 μM 浓度下对 ALK5 的抑制活性为 80.8%，IC50 值为 4.69 μM，但对 p38α MAP 激酶没有抑制活性（在 10 μM 浓度下抑制率为-1.94%）。
