期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 54, 期 1, 页码 201-210出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm1010995
关键词
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Aurora kinases are cell cycle regulated serine/threonine kinases that have been linked to cancer Compound 1 was identified as a potent Aurora inhibitor but lacked oral bioavailability Optimization of 1 led to the discovery of a series of fluoroamine and deuterated analogues, exemplified by compound 25, with an improved pharmacokinetic profile We found that blocking oxidative metabolism at the benzylic position and decreasing the basicity of the amine are important to obtaining compounds with good biological profiles and oral bioavailability
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