新型吡咯并[2,1-f][1,2,4]三嗪作为强效p38α丝裂原活化蛋白激酶抑制剂的合成及构效关系研究
Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38 alpha MAP kinase inhibitors.
作者信息
Wrobleski Stephen T, Lin Shuqun, Hynes John, Wu Hong, Pitt Sidney, Shen Ding Ren, Zhang Rosemary, Gillooly Kathleen M, Shuster David J, McIntyre Kim W, Doweyko Arthur M, Kish Kevin F, Tredup Jeffrey A, Duke Gerald J, Sack John S, McKinnon Murray, Dodd John, Barrish Joel C, Schieven Gary L, Leftheris Katerina
机构信息
Department of Immunology Chemistry, Bristol-Myers Squibb, Princeton, NJ 08543-4000, USA.
出版信息
Bioorg Med Chem Lett. 2008 Apr 15;18(8):2739-44. doi: 10.1016/j.bmcl.2008.02.067. Epub 2008 Mar 4.
A novel series of compounds based on the pyrrolo[2,1-f][1,2,4]triazine ring system have been identified as potent p38 alpha MAP kinase inhibitors. The synthesis, structure-activity relationships (SAR), and in vivo activity of selected analogs from this class of inhibitors are reported. Additional studies based on X-ray co-crystallography have revealed that one of the potent inhibitors from this series binds to the DFG-out conformation of the p38 alpha enzyme.
一系列基于吡咯并[2,1-f][1,2,4]三嗪环系统的新型化合物已被鉴定为有效的p38α丝裂原活化蛋白激酶抑制剂。本文报道了这类抑制剂中选定类似物的合成、构效关系（SAR）及体内活性。基于X射线共结晶学的进一步研究表明，该系列中的一种强效抑制剂与p38α酶的DFG-out构象结合。
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