Medicinal Chemistry, Pfizer, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
Bioorg Med Chem Lett. 2011 Oct 1;21(19):5952-6. doi: 10.1016/j.bmcl.2011.07.069. Epub 2011 Jul 26.
We report here the synthesis and SAR of a new series of thieno[3,2-d]pyrimidines as potent Tpl2 kinase inhibitors. The proposed binding mode suggests the potential flipped binding mode depending on the substitution. Biacore studies show evidence of binding of these molecules to the protein kinase. The kinome inhibition profile of these molecules suggests good selectivity.
我们在此报告了一系列新型噻吩并[3,2-d]嘧啶的合成和构效关系研究,这些化合物是有效的 Tpl2 激酶抑制剂。所提出的结合模式表明,根据取代基的不同,可能存在翻转的结合模式。Biacore 研究表明这些分子与蛋白激酶的结合证据。这些分子的激酶组抑制谱表明它们具有良好的选择性。