3-Cyano-6-(5-methyl-3-pyrazoloamino) pyridines (Part 2): A dual inhibitor of Aurora kinase and tubulin polymerization

详细信息    查看全文

• 作者：Masahiko Morioka ^{sakura-saku1103@rondo.ocn.ne.jp}
• 关键词：Aurora kinase inhibitor ; Anti-cancer reagent ; Tubulin polymerization inhibitor
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 December 2016
• 年：2016
• 卷：26
• 期：24
• 页码：5860-5862
• 全文大小：1221 K
• 卷排序：26

文摘

A new class of a dual inhibitor of Aurora kinase and tubulin polymerization was created by introducing various substituted phenoxyethylamino or pyridyloxyethylamino groups to the 2-position of 3-cyano-4-methyl-6-(5-methyl-3-pyrazoloamino)-pyridine. Compound 3g exhibited Aurora kinase inhibition, excellent protein kinase selectivity to Aurora kinase in comparison with 66 other kinases, inhibition of phosphorylation of Ser10 of histone H3 as an Aurora kinase inhibitor, inhibition of tubulin polymerization in vitro, good cell membrane permeability, and a good PK profile. Therefore compound 3g was effective in some antitumor mouse models at a dose of 30 mg/kg po qd.