Synthesis and multiparametric evaluation of thiadiazoles and oxadiazoles as diacylglycerol acyltransferase type 1 inhibitors. Issue 1 (1st January 2016)

• Record Type: Journal Article
• Authors: Mougenot, Patrick; Namane, Claudie; Fett, Eykmar; Goumy, Florence; Dadji-Faïhun, Rommel; Langot, Gwladys; Monseau, Catherine; Onofri, Bénédicte; Pacquet, François; Pascal, Cécile; Crespin, Olivier; Ben-Hassine, Majdi; Ragot, Jean-Luc; Van-Pham, Thao; Philippo, Christophe; Chatelain-Egger, Florence; Péron, Philippe; Le Bail, Jean-Christophe; Guillot, Etienne; Chamiot-Clerc, Philippe; Chabanaud, Marie-Aude; Pruniaux, Marie-Pierre; Ménegotto, Jérôme; Schmidt, Friedemann; Venier, Olivier; Viviani, Fabrice; Nicolai, Eric
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 1(2016)
• Page Start: 25
• Page End: 32
• Publication Date: 2016-01-01
• Subjects: DBU 1, 8-diazabicyclo[5.4.0]undec-7-ene -- DCM dichloromethane -- DIAD diisopropylazodicarboxylate -- DMF dimethylformamide -- CDI carbonyldiimidazole -- met. lia. metabolic liability -- MC methylcellulose -- ND not determined -- PK pharmacokinetic -- PyBroP bromotrispyrrolidinophosphonium hexafluorophosphonate -- sol. solubility -- T tween -- TEA triethylamine -- TFA trifluoroacetic acid -- TG triglycerides -- THF tetrahydrofuran; Diacylglycerol acyltransferase type 1 -- DGAT-1 inhibitors -- Thiadiazole -- Oxadiazole -- Solubility -- Metabolic lability; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.11.046
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Chemical modulation of a formerly disclosed DGAT-1 inhibitor resulted in the identification of a compound with a suitable profile for preclinical development. Optimisation of solubility is discussed and a PK/PD study is presented.