Substituted quinolines as noncovalent proteasome inhibitors.

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 5.4?M), representing a new class of nonpeptidic, noncovalent proteasome inhibitors.

SUBMITTER: McDaniel TJ 

PROVIDER: S-EPMC5724766 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature