Substituted 3-amino-5-phenylbenzamide compounds as covalent inhibitors of enhancer zeste homolog 2 (ezh2) and proteolysis-targeting chimeric derivatives thereof (protacs) that induce degradation of ezh2

Abstract

Disclosed are covalent inhibitors of enhancer zeste homolog 2 (EZH2) which may be utilized as EZH2 targeting agents. The disclosed compounds may be characterized as substituted 3-amino-5-phenylbenzamide compounds. The disclosed compounds may be utilized as covalent inhibitors of EZH2 and further may be derivatized to form proteolysis-targeting chimeric molecules (PROTACs) that target EZH2 for degradation. The disclosed compounds and PROTACs may be used in pharmaceutical compositions and methods for treating cell proliferative disorders associated with EZH2 activity, such as cancer.