title: Evaluation of Michael-type acceptor reactivity of 5-benzylidenebarbiturates, 5-benzylidenerhodanines, and related heterocycles using NMR.
abstract: Despite existing experimental and computational tools to assess the risk, the non-specific chemical modification of protein thiol groups remains a significant source of false-positive hits, particularly in academic drug discovery. Herein, we describe the application of a simple NMR method in a systematic study on the reactivity of 5-benzylidenebarbiturates, 5-benzylidenerhodanines, and their related oxo-heterocycles, which have been associated with numerous biological activities and have recently gained a reputation as unselective promiscuous binders. Using this method, we confirmed the reactivity of 5-benzylidenebarbiturates, which are known to easily form Michael adducts with nucleophiles. In contrast, 5-benzylidene five-membered oxo-heterocycles revealed almost insignificant reactivity. We can conclude that the distinct binding profile of the most controversial compounds, 5-benzylidenerhodanines, is not necessarily related to their unspecific Michael acceptor reactivity.
authors.forename: Emilija
authors.initials: E
authors.lastname: Arsovska
authors.forename: Jurij
authors.initials: J
authors.lastname: Trontelj
authors.forename: Nace
authors.initials: N
authors.lastname: Zidar
authors.forename: Tihomir
authors.initials: T
authors.lastname: Tomašić
authors.forename: Lucija Peterlin
authors.initials: LP
authors.lastname: Mašič
authors.forename: Danijel
authors.initials: D
authors.lastname: Kikelj
authors.forename: Janez
authors.initials: J
authors.lastname: Plavec
authors.forename: Anamarija
authors.initials: A
authors.lastname: Zega