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http://dx.doi.org/10.5012/bkcs.2014.35.7.2123

3,5-Bis(aminopyrimidinyl)indole Derivatives: Synthesis and Evaluation of Pim Kinase Inhibitory Activities  

Lee, Jinho (Department of Chemistry, Keimyung University)
More, Kunal N. (Department of Chemistry, Keimyung University)
Yang, Seun-Ah (The Center for Traditional Microorganism Resources (TMR), Keimyung University)
Hong, Victor S. (Department of Chemistry, Keimyung University)
Publication Information
Bulletin of the Korean Chemical Society / v.35, no.7, 2014 , pp. 2123-2129 More about this Journal
Abstract
Pim kinases are promising targets in the treatment of hematopoietic and solid cancers. Meridianin C was chosen as a starting point to discover novel pim kinase inhibitors. Using known pim kinase's structural information, aminopyrimidine was introduced to provide the hydrogen-bonding interactions with the conserved lysine residue in the ATP binding pocket of all three Pim kinases. Synthesized 3,5-bis(aminopyrimidinyl)indole derivatives showed pan-pim inhibitory activity. Aminoalkyl substituent was attached on the aminopyrimidine to further enhance the potency and physicochemical properties of compound. The research reveals a significative way of designing compounds with high potency and kinase selectivity for pan-pim kinases.
Keywords
3,5-Bis(aminopyrimidinyl)indole; Pim kinase; Inhibitor;
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