Diversity-oriented synthesis of a cytisine-inspired pyridone library leading to the discovery of novel inhibitors of Bcl-2.
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.
Marcaurelle
Lisa A
LA
Infinity Pharmaceuticals, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Johannes
Charles
C
Yohannes
Daniel
D
Tillotson
Bonnie P
BP
Mann
David
D