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.
Department of Comparative Medicine, College of Veterinary Medicine, The University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA.
T Wayne
TW
Schultz
Jason W
JW
Yarbrough
Robert S
RS
Hunter
Aynur O
AO
Aptula
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