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ID: ALA1938352

Journal: Bioorg Med Chem Lett

Title: Discovery of potent and liver-targeted stearoyl-CoA desaturase (SCD) inhibitors in a bispyrrolidine series.

Authors: Lachance N, Gareau Y, Guiral S, Huang Z, Isabel E, Leclerc JP, Léger S, Martins E, Nadeau C, Oballa RM, Ouellet SG, Powell DA, Ramtohul YK, Tranmer GK, Trinh T, Wang H, Zhang L.

Abstract: Inhibition of stearoyl-CoA desaturase (SCD) activity represents a potential novel mechanism for the treatment of metabolic disorders including obesity and type II diabetes. To circumvent skin and eye adverse events observed in rodents with systemically-distributed SCD inhibitors, our research efforts have been focused on the search for new and structurally diverse liver-targeted SCD inhibitors. This work has led to the discovery of novel, potent and structurally diverse liver-targeted bispyrrolidine SCD inhibitors. These compounds possess suitable cellular activity and pharmacokinetic properties to inhibit liver SCD activity in a mouse pharmacodynamic model.

CiteXplore: 22209206

DOI: 10.1016/j.bmcl.2011.12.002