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

作者：Lee Jinho^*; More Kunal N; Yang Seun Ah; Hong Victor S

来源：BULLETIN OF THE KOREAN CHEMICAL SOCIETY, 2014, 35(7): 2123-2129.

DOI：10.5012/bkcs.2014.35.7.2123

• 3,5-Bis(aminopyrimidinyl)indole
• Pim kinase
• Inhibitor

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.

• 出版日期2014-7-20