Verification of the structural alerts for Michael acceptors.
A diverse series of polarized alpha,beta-unsaturated and related compounds were evaluated for reactivity with a spectrophotometric assay using the sulfhydryl group in the form of the cysteine residue of the tripeptide GSH as a model nucleophile. The reactive end point (RC 50) calculations were compared to previously described structural alerts based on conventional organic chemistry. This comparison focused on polarized alpha,beta-unsaturates, including ones containing an aldehyde, ketone, ester, sulfoxide, sulfone, sulfonate, nitro, or cyano moiety as well as ortho- and para-pyridino compounds and ortho- and para-quinones. The alerts were coded by substructure and are available in open-source software ( http://sourceforge.net/projects/chemeval). Comparisons of reactivity between selected analogues revealed that only the polarized alpha,beta-unsaturates were reactive. These results verified the coded structural alerts that define the applicability domain for Michael acceptor electrophiles.
Schultz
T Wayne
TW
Department of Comparative Medicine, College of Veterinary Medicine, The University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA.
Yarbrough
Jason W
JW
Hunter
Robert S
RS
Aptula
Aynur O
AO
D000475:Alkenes / Q000737:chemistry*; D000480:Alkynes / Q000737:chemistry*; D003198:Computer Simulation; D003545:Cysteine / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D013053:Spectrophotometry
D000475:Alkenes; D000480:Alkynes; D003545:Cysteine