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

Serge Léger; W Cameron Black; Denis Deschenes; Sarah Dolman; Jean-Pierre Falgueyret; Marc Gagnon; Sébastien Guiral; Zheng Huang; Jocelyne Guay; Yves Leblanc; Chun-Sing Li; Frédéric Massé; Renata Oballa; Lei Zhang

doi:10.1016/j.bmcl.2009.11.111

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

Bioorg Med Chem Lett. 2010 Jan 15;20(2):499-502. doi: 10.1016/j.bmcl.2009.11.111. Epub 2009 Nov 26.

Authors

Serge Léger¹, W Cameron Black, Denis Deschenes, Sarah Dolman, Jean-Pierre Falgueyret, Marc Gagnon, Sébastien Guiral, Zheng Huang, Jocelyne Guay, Yves Leblanc, Chun-Sing Li, Frédéric Massé, Renata Oballa, Lei Zhang

Affiliation

¹ Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe-Claire-Dorval, Québec, Canada H9R 4P8.

PMID: 20004097
DOI: 10.1016/j.bmcl.2009.11.111

Abstract

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.

MeSH terms

Administration, Oral
Animals
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacokinetics
Mice
Microsomes, Liver / metabolism
Pyridazines / chemical synthesis*
Pyridazines / chemistry
Pyridazines / pharmacokinetics
Rats
Stearoyl-CoA Desaturase / antagonists & inhibitors*
Stearoyl-CoA Desaturase / metabolism
Structure-Activity Relationship
Thiadiazoles / chemical synthesis*
Thiadiazoles / chemistry
Thiadiazoles / pharmacokinetics

Substances

Enzyme Inhibitors
MF 438
Pyridazines
Thiadiazoles
pyridazine
Stearoyl-CoA Desaturase