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

• Published in: Bioorganic & medicinal chemistry letters 2010-01, Vol.20 (2), p.499-502
• Main Authors: Léger, Serge, Black, W. Cameron, Deschenes, Denis, Dolman, Sarah, Falgueyret, Jean-Pierre, Gagnon, Marc, Guiral, Sébastien, Huang, Zheng, Guay, Jocelyne, Leblanc, Yves, Li, Chun-Sing, Massé, Frédéric, Oballa, Renata, Zhang, Lei
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Bioavailable; Biological and medical sciences; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacokinetics; General and cellular metabolism. Vitamins; Medical sciences; Mice; Microsomes, Liver - metabolism; Pharmacology. Drug treatments; Pyridazine; Pyridazines - chemical synthesis; Pyridazines - chemistry; Pyridazines - pharmacokinetics; Rats; SCD inhibitor; Stearoyl-CoA; Stearoyl-CoA Desaturase - antagonists & inhibitors; Stearoyl-CoA Desaturase - metabolism; Structure-Activity Relationship; Thiadiazole; Thiadiazoles - chemical synthesis; Thiadiazoles - chemistry; Thiadiazoles - pharmacokinetics
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.11.111

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 which exhibits good pharmacokinetics and metabolic stability. 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.