title: Conversion of systemically-distributed triazole-based stearoyl-CoA desaturase (SCD) uHTS hits into liver-targeted SCD inhibitors.
abstract: It has been demonstrated that once-a-day dosing of systemically-distributed SCD inhibitors leads to adverse events in eye and skin. Herein, we describe our efforts to convert a novel class of systemically-distributed potent triazole-based uHTS hits into liver-targeted SCD inhibitors as a means to circumvent chronic toxicity.
authors.affiliation: Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, 16711 TransCanada Hwy, Kirkland, Quebec, Canada H9H 3L1. j.philippe.leclerc@gmail.com
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Leclerc
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Falgueyret
authors.forename: Mélina
authors.initials: M
authors.lastname: Girardin
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Guay
authors.forename: Sébastien
authors.initials: S
authors.lastname: Guiral
authors.forename: Zheng
authors.initials: Z
authors.lastname: Huang
authors.forename: Chun Sing
authors.initials: CS
authors.lastname: Li
authors.forename: Renata
authors.initials: R
authors.lastname: Oballa
authors.forename: Yeeman K
authors.initials: YK
authors.lastname: Ramtohul
authors.forename: Kathryn
authors.initials: K
authors.lastname: Skorey
authors.forename: Paul
authors.initials: P
authors.lastname: Tawa
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D051381:Rats; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors*; D014018:Tissue Distribution; D014230:Triazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D014230:Triazoles; D013230:Stearoyl-CoA Desaturase