Substituted quinolines as noncovalent proteasome inhibitors

Bioorg Med Chem. 2016 Jun 1;24(11):2441-2450. doi: 10.1016/j.bmc.2016.04.005.

Tanner J McDaniel ¹, Theresa A Lansdell ¹, Amila A Dissanayake ¹, Lauren M Azevedo ¹, Jacob Claes ¹, Aaron L Odom ², Jetze J Tepe ³

Affiliations

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.

PMID: 27112450 DOI: 10.1016/j.bmc.2016.04.005

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.

Keywords

Inhibitors; Noncovalent; Proteasome; Quinolines.

Name
Email *

	Sorry, but the email address you supplied was invalid.