Synthesis and biological activity of a potent and orally bioavailable SCD inhibitor (MF-438)

A series of stearoyl-CoA desaturase 1 (SCD1) inhibitors were developed. Investigations of enzyme potency and metabolism led to the identification of the thiadiazole–pyridazine derivative MF-438 as a potent SCD1 inhibitor. MF-438 exhibits good pharmacokinetics and metabolic stability, thereby serving as a valuable tool for further understanding the role of SCD inhibition in biological and pharmacological models of diseases related to metabolic disorders.

Graphical abstractA series of stearoyl-CoA desaturase 1 (SCD1) inhibitors were developed. Investigations of enzyme potency and metabolism led to the identification of the thiadiazole–pyridazine derivative MF-438 as a potent SCD1 inhibitor which exhibits good pharmacokinetics and metabolic stability.Figure optionsDownload full-size imageDownload as PowerPoint slide