Tunable Methacrylamides for Covalent Ligand Directed Release Chemistry.
Journal
Journal of the American Chemical Society
ISSN: 1520-5126
Titre abrégé: J Am Chem Soc
Pays: United States
ID NLM: 7503056
Informations de publication
Date de publication:
07 04 2021
07 04 2021
Historique:
pubmed:
26
3
2021
medline:
26
3
2021
entrez:
25
3
2021
Statut:
ppublish
Résumé
Targeted covalent inhibitors are an important class of drugs and chemical probes. However, relatively few electrophiles meet the criteria for successful covalent inhibitor design. Here we describe α-substituted methacrylamides as a new class of electrophiles suitable for targeted covalent inhibitors. While typically α-substitutions inactivate acrylamides, we show that hetero α-substituted methacrylamides have higher thiol reactivity and undergo a conjugated addition-elimination reaction ultimately releasing the substituent. Their reactivity toward thiols is tunable and correlates with the p
Identifiants
pubmed: 33761747
doi: 10.1021/jacs.0c10644
pmc: PMC8041284
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4979-4992Références
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