Verification of the structural alerts for Michael acceptors.

Abstract:

: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.

journal_name

Chem Res Toxicol

authors

Schultz TW,Yarbrough JW,Hunter RS,Aptula AO

doi

10.1021/tx700212u

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

1359-63

issue

9

eissn

0893-228X

issn

1520-5010

journal_volume

20

pub_type

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