title: Synthesis and multiparametric evaluation of thiadiazoles and oxadiazoles as diacylglycerol acyltransferase type 1 inhibitors.
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.
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mougenot
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Claudie
authors.initials: C
authors.lastname: Namane
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Eykmar
authors.initials: E
authors.lastname: Fett
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Goumy
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Rommel
authors.initials: R
authors.lastname: Dadji-Faïhun
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Gwladys
authors.initials: G
authors.lastname: Langot
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Monseau
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Onofri
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: François
authors.initials: F
authors.lastname: Pacquet
authors.affiliation: Sanofi-aventis R&D, 69280 Marcy-l'Etoile, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Pascal
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Crespin
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Majdi
authors.initials: M
authors.lastname: Ben-Hassine
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Ragot
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Thao
authors.initials: T
authors.lastname: Van-Pham
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Philippo
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Chatelain-Egger
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Péron
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Le Bail
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Guillot
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chamiot-Clerc
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Marie-Aude
authors.initials: MA
authors.lastname: Chabanaud
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Pruniaux
authors.affiliation: Evotec, 31036 Toulouse, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Ménegotto
authors.affiliation: Sanofi-aventis Deutschland GmbH, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Schmidt
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Venier
authors.affiliation: GlaxoSmithKline, 91951 Les Ulis, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Viviani
authors.affiliation: Sanofi-aventis R&D, 91385 Chilly-Mazarin, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Nicolai
mesh_terms: D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D013830:Thiadiazoles; C494881:DGAT1 protein, human; D051048:Diacylglycerol O-Acyltransferase
keywords: DGAT-1 inhibitors; Diacylglycerol acyltransferase type 1; Metabolic lability; Oxadiazole; Solubility; Thiadiazole