Tanner J McDaniel1, Theresa A Lansdell1, Amila A Dissanayake1, Lauren M Azevedo1, Jacob Claes1, Aaron L Odom2, Jetze J Tepe3. 1. Department of Chemistry, Michigan State University, East Lansing, MI 48824, United States. 2. Department of Chemistry, Michigan State University, East Lansing, MI 48824, United States. Electronic address: Odom@chemistry.msu.edu. 3. Department of Chemistry, Michigan State University, East Lansing, MI 48824, United States. Electronic address: Tepe@chemistry.msu.edu.
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.
Screening of a library of diverse heterocyclic scaffolds identified substituted n class="Chemical">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.
Authors: Lauren M Azevedo; Theresa A Lansdell; Jacob R Ludwig; Robert A Mosey; Daljinder K Woloch; Dillon P Cogan; Gregory P Patten; Michael R Kuszpit; Jason S Fisk; Jetze J Tepe Journal: J Med Chem Date: 2013-07-03 Impact factor: 7.446
Authors: Małgorzata Giżyńska; Julia Witkowska; Przemysław Karpowicz; Rafał Rostankowski; Estrella S Chocron; Andrew M Pickering; Pawel Osmulski; Maria Gaczynska; Elżbieta Jankowska Journal: J Med Chem Date: 2018-12-03 Impact factor: 7.446