3-Cyano-6-(5-methyl-3-pyrazoloamino)pyridines: Selective Aurora A kinase inhibitors

被引：25

作者：

Ando, Ryoichi ^{[1
]}

Ikegami, Hiroshi ^{[1
]}

Sakiyama, Makoto ^{[1
]}

Ooike, Shinsuke ^{[2
]}

Hayashi, Masayuki ^{[2
]}

Fujino, Yasuhiro ^{[2
]}

Abe, Daisuke ^{[1
]}

Nakamura, Hideo ^{[2
]}

Mishina, Tadashi ^{[1
]}

Kato, Harutoshi ^{[3
]}

Iwase, Yumiko ^{[4
]}

Tomozane, Hideo ^{[1
]}

Morioka, Masahiko ^{[1
]}

机构：

[1] Mitsubishi Tanabe Pharma Corp, Med Chem Res Labs, Aoba Ku, Yokohama, Kanagawa 2270033, Japan

[2] Mitsubishi Tanabe Pharma Corp, Pharmacol Res Labs, Aoba Ku, Yokohama, Kanagawa 2270033, Japan

[3] Mitsubishi Tanabe Pharma Corp, DMPK Res Labs, Toda, Saitama 3358505, Japan

[4] Mitsubishi Tanabe Pharma Corp, Safety Res Labs, Chiba 2920818, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 15期

关键词：

Aurora kinase; Cyanopyridine; Aminopyrazole; VX-680; POTENT; ABL;

D O I：

10.1016/j.bmcl.2010.04.119

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2010 Published by Elsevier Ltd.

引用

页码：4709 / 4711

页数：3

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