Bicyclic heteroaryl inhibitors of stearoyl-CoA desaturase: From systemic to liver-targeting inhibitors

Optimization of a lead thiazole amide MF-152 led to the identification of potent bicyclic heteroaryl SCD1 inhibitors with good mouse pharmacokinetic profiles. In a view to target the liver for efficacy and to avoid SCD1 inhibition in the skin and eyes where adverse effects were previously observed in rodents, representative systemically-distributed SCD1 inhibitors were converted into liver-targeting SCD1 inhibitors.

Graphical abstractNovel and potent bicyclic heteroaryl SCD inhibitors were identified from optimization of a lead thiazole amide inhibitor, MF-152. In order to target the liver and to minimize systemic exposure to avoid skin and eye adverse events, representative systemically-distributed inhibitors were converted into liver-targeting SCD inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide