Medicinal Chemistry Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Aoba-ku, Yokohama 227-0033, Japan.
Bioorg Med Chem Lett. 2010 Aug 1;20(15):4709-11. doi: 10.1016/j.bmcl.2010.04.119. Epub 2010 May 25.
A new class of Aurora A kinase inhibitor was created by transforming 4-(5-methyl-3-pyrazoloamino)pyrimidine moiety of VX-680 to 3-cyano-6-(5-methyl-3pyrazoloamino)pyridine. Compound 6 exhibited a potent Aurora A kinase inhibitory activity, excellent selectivity to Aurora B kinase and other 60 kinases, good cell permeability and good PK profile. Therefore compound 6 was effective in antitumor mice model at a dose of 30 mg/kg po qd without decrease of body weight.
一种新型的 Aurora A 激酶抑制剂是通过将 VX-680 中的 4-(5-甲基-3-吡唑基氨基)嘧啶部分转化为 3-氰基-6-(5-甲基-3-吡唑基氨基)吡啶而合成的。化合物 6 表现出很强的 Aurora A 激酶抑制活性，对 Aurora B 激酶和其他 60 种激酶具有优异的选择性，细胞通透性良好，PK 特征良好。因此，化合物 6 在 30mg/kg po qd 的剂量下在抗肿瘤小鼠模型中有效，且体重无下降。
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