Pyrimidine tricyclic enone derivatives for inhibition of rorγ and other uses

Disclosed herein are compounds of the formulas: as well as analogs thereof, wherein the variables are defined herein. Also provided are pharmaceutical compositions thereof. In some aspects, the compounds and compositions provided herein may be used to inhibit RORγ and/or reduce the expression of IL-17. The compounds described herein have good RORγ inhibitory activity, despite having 'natural configuration' at the stereocenters C4, C5, and C10 in formula (I). Also provided are methods of administering compounds and composition provided herein to a patient in need thereof, for example, for the treatment or prevention of diseases or disorders associated with inflammation or autoimmune disorders.