Diversity-oriented synthesis of a cytisine-inspired pyridone library leading to the discovery of novel inhibitors of Bcl-2.

Basic Information

ID: ALA1138601

Journal: Bioorg Med Chem Lett

Title: Diversity-oriented synthesis of a cytisine-inspired pyridone library leading to the discovery of novel inhibitors of Bcl-2.

Authors: Marcaurelle LA, Johannes C, Yohannes D, Tillotson BP, Mann D.

Abstract: Four enantiopure cytisine-inspired scaffolds can be accessed via a versatile pyrrolidine template derived from a stereocontrolled [3+2] azomethine ylide-alkene cycloaddition. Differential ester protection allows for the selective formation of either a bridged bicyclic or tricyclic scaffold via pyridone cyclization. Solid-phase diversification of the pyridone scaffolds yielded a diverse library of 15,000 compounds enabling the discovery of a novel class of Bcl-2 inhibitors.

CiteXplore: 19329314

DOI: 10.1016/j.bmcl.2009.03.037

Patent ID: