Conversion of systemically-distributed triazole-based stearoyl-CoA desaturase (SCD) uHTS hits into liver-targeted SCD inhibitors

Study to convert systemically-distributed SCD uHTS hits into liver-targeting inhibitors is described. It has been demonstrated that once-a-day dosing of systemically-distributed SCD inhibitors leads to adverse events in eye and skin. Herein, we describe our efforts to convert a novel class of systemically-distributed potent triazole-based uHTS hits into liver-targeted SCD inhibitors as a means to circumvent chronic toxicity.