Department of Medicinal Chemistry, Ambit Biosciences Corporation, 4215 Sorrento Valley Boulevard, San Diego, CA 92121, United States.
Bioorg Med Chem Lett. 2011 Sep 15;21(18):5296-300. doi: 10.1016/j.bmcl.2011.07.027. Epub 2011 Jul 14.
The synthesis and SAR for a novel series of pyrrolotriazines as pan-Aurora kinase inhibitors are described. Optimization of the cyclopropane carboxamide terminus of lead compound 1 resulted in analogs with high cellular activity and improved rat PK profiles. Notably, compound 17l demonstrated tumor growth inhibition in a mouse xenograft model.
本文描述了一系列新型吡咯并三嗪类作为泛 Aurora 激酶抑制剂的合成和构效关系研究。通过对先导化合物 1 的环丙烷羧酰胺末端进行优化，得到了具有高细胞活性和改善的大鼠 PK 特征的类似物。值得注意的是，化合物 17l 在小鼠异种移植模型中显示出肿瘤生长抑制作用。
