Substituted quinolines as noncovalent proteasome inhibitors.
Bioorg Med Chem
; 24(11): 2441-50, 2016 06 01.
Article
em En
| MEDLINE
| ID: mdl-27112450
ABSTRACT
Screening of a library of diverse heterocyclic scaffolds identified substituted quinolines as inhibitors of the human proteasome. The heterocyclic library was prepared via a novel titanium-catalyzed multicomponent coupling reaction, which rendered a diverse set of isoxazoles, pyrimidines, pyrroles, pyrazoles and quinolines. SAR of the parent lead compound indicated that hydrophobic residues on the benzo-moiety significantly improved potency. Lead compound 25 inhibits the chymotryptic-like proteolytic activity of the proteasome (IC50 5.4µM), representing a new class of nonpeptidic, noncovalent proteasome inhibitors.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
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Complexo de Endopeptidases do Proteassoma
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Inibidores de Proteassoma
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article