Identification of Potent and Selective Diphenylpropanamide RORγ Inhibitors

Retinoic acid-related orphan receptor RORγt plays a pivotal role in the differentiation of T H 17 cells. Antagonizing RORγt transcriptional activity is a potential means to treat T H 17-related autoimmune diseases. Herein, we describe the identification of a series of diphenylpropanamides as novel and selective RORγ antagonists. Diphenylpropanamide 4n inhibited the transcriptional activity of RORγt, but not RORα, in cells. In addition, it suppressed human T H 17 cell differentiation at submicromolar concentrations.