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首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >Two classes of p38alpha MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes.
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Two classes of p38alpha MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes.

机译:具有共同的二苯醚核心但表现出不同的结合模式的两类p38alpha MAP激酶抑制剂。

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摘要

Two new classes of diphenylether inhibitors of p38alpha MAP kinase are described. Both chemical classes are based on a common diphenylether core that is identified by simulated fragment annealing as one of the most favored chemotypes within a prominent hydrophobic pocket of the p38alpha ATP-binding site. In the fully elaborated molecules, the diphenylether moiety acts as an anchor occupying the deep pocket, while polar extensions make specific interactions with either the adenine binding site or the phosphate binding site of ATP. The synthesis, crystallographic analysis, and biological activity of these p38alpha inhibitors are discussed.
机译:描述了两类新的p38alpha MAP激酶的二苯醚抑制剂。两种化学类别均基于共同的二苯醚核心,该核心已通过模拟片段退火鉴定为p38alpha ATP结合位点显着疏水口袋中最优选的化学型之一。在充分加工的分子中,二苯醚部分充当占据深口袋的锚点,而极性延伸与ATP的腺嘌呤结合位点或磷酸盐结合位点形成特异性相互作用。讨论了这些p38alpha抑制剂的合成,晶体学分析和生物学活性。

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