posted on 2006-11-23, 00:00authored byHoward Bregman, Eric Meggers
Cyclopentadienyl half-sandwich ruthenium complexes have been demonstrated to be promising scaffolds as protein kinase inhibitors. In
order to rapidly identify derivatives which display modified pharmacological properties, we developed the synthesis of an organoruthenium
compound bearing an N-succinimidyl ester at the cyclopentadienyl moiety. The quenching of this activated ester with a library of primary
amines, followed by testing of the resulting amide library, led to the identification of organometallic Pim-1 and GSK-3 inhibitors with improved
potencies and kinase selectivities.