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