Evaluation of Michael-type acceptor reactivity of 5-benzylidenebarbiturates, 5-benzylidenerhodanines, and related heterocycles using NMR.

摘要: Despite existing experimental and computational tools to assess the risk, non-specific chemical modification of protein thiol groups remains a significant source false-positive hits, particularly in academic drug discovery. Herein, we describe application simple NMR method systematic study on reactivity 5-benzylidenebarbiturates, 5-benzylidenerhodanines, their related oxo-heterocycles, which have been associated with numerous biological activities recently gained reputation as unselective promiscuous binders. Using this method, confirmed are known easily form Michael adducts nucleophiles. In contrast, 5-benzylidene five-membered oxo-heterocycles revealed almost insignificant reactivity. We can conclude that distinct binding profile most controversial compounds, is not necessarily unspecific acceptor