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Bioorg Med Chem Lett. 2010 Jan 1;20(1):334-7. doi: 10.1016/j.bmcl.2009.10.103. Epub 2009 Oct 29.
We describe structure-based optimization of a series of novel 2,4-diaminopyrimidine MK2 inhibitors. Co-crystal structures (see accompanying Letter) demonstrated a unique inhibitor binding mode. Resulting inhibitors had IC(50) values as low as 19nM and moderate selectivity against a kinase panel. Compounds 15, 31a, and 31b inhibit TNFalpha production in peripheral human monocytes.
我们描述了一系列新型 2,4-二氨基嘧啶 MK2 抑制剂的基于结构的优化。共晶结构（见随附的信）证明了一种独特的抑制剂结合模式。由此产生的抑制剂的 IC50 值低至 19nM，对激酶谱具有中等选择性。化合物 15、31a 和 31b 抑制外周人单核细胞中 TNFalpha 的产生。
