Identification and structure–activity relationships of substituted pyridones as inhibitors of Pim-1 kinase

…, T Appleby, H Walker, T Vo, N Yao, R Hamatake…

Index: Cheney, I. Wayne; Yan, Shunqi; Appleby, Todd; Walker, Heli; Vo, Todd; Yao, Nanhua; Hamatake, Robert; Hong, Zhi; Wu, Jim Z. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 6 p. 1679 - 1683

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Citation Number: 97

Abstract

A novel series of highly potent substituted pyridone Pim-1 kinase inhibitors is described. Structural requirements for in vitro activity are outlined as well as a complex crystal structure with the most potent Pim-1 inhibitor reported (IC50= 50nM). A hydrogen bond matrix involving the Pim-1 inhibitor, two water molecules, and the catalytic core, together with a potential weak hydrogen bond between an aromatic hydrogen on the R1 phenyl ring and ...