title: Synthesis and biological activity of a potent and orally bioavailable SCD inhibitor (MF-438).
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.
authors.affiliation: Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe-Claire-Dorval, Québec, Canada H9R 4P8.
authors.forename: Serge
authors.initials: S
authors.lastname: Léger
authors.forename: W Cameron
authors.initials: WC
authors.lastname: Black
authors.forename: Denis
authors.initials: D
authors.lastname: Deschenes
authors.forename: Sarah
authors.initials: S
authors.lastname: Dolman
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Falgueyret
authors.forename: Marc
authors.initials: M
authors.lastname: Gagnon
authors.forename: Sébastien
authors.initials: S
authors.lastname: Guiral
authors.forename: Zheng
authors.initials: Z
authors.lastname: Huang
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Guay
authors.forename: Yves
authors.initials: Y
authors.lastname: Leblanc
authors.forename: Chun-Sing
authors.initials: CS
authors.lastname: Li
authors.forename: Frédéric
authors.initials: F
authors.lastname: Massé
authors.forename: Renata
authors.initials: R
authors.lastname: Oballa
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004791:Enzyme Inhibitors; C548713:MF 438; D011724:Pyridazines; D013830:Thiadiazoles; C062482:pyridazine; D013230:Stearoyl-CoA Desaturase