A 13C NMR approach to categorizing potential limitations of alpha,beta-unsaturated carbonyl systems in drug-like molecules.

Compounds that contain an alpha,beta-unsaturated carbonyl moiety are often flagged as potential Michael acceptors. All alpha,beta-unsaturated carbonyl moieties are not equivalent, however, and we sought to better understand this system and its potential implications in drug-like molecules. Measurement of the (13)C NMR shift of the beta-carbon and correlation to in vitro results allowed compounds in our collection to be categorized as potential Michael acceptors, potential substrates for NADPH, or as photoisomerizable.