title: Identification of 2-aminooxazole amides as acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1) inhibitors through scaffold hopping strategy.
abstract: A scaffold hopping strategy was successfully applied in discovering 2-aminooxazole amides as potent DGAT1 inhibitors for the treatment of dyslipidemia. Further optimization in potency and PK properties resulted in a lead series with oral in vivo efficacy in a mouse postprandial triglyceridemia (PPTG) assay.
authors.affiliation: Discovery Chemistry, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: hyunjin.kim@merck.com.
authors.forename: Hyunjin M
authors.initials: HM
authors.lastname: Kim
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Smith
authors.forename: Jae-Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Caplen
authors.forename: Tin Yau
authors.initials: TY
authors.lastname: Chan
authors.forename: Brian A
authors.initials: BA
authors.lastname: McKittrick
authors.forename: John A
authors.initials: JA
authors.lastname: Cook
authors.forename: Margaret
authors.initials: M
authors.lastname: van Heek
authors.forename: Jean
authors.initials: J
authors.lastname: Lachowicz
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D010080:Oxazoles / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood*
chemical_list: C518811:2-aminooxazole; D000577:Amides; D004791:Enzyme Inhibitors; D010080:Oxazoles; D014280:Triglycerides; D051048:Diacylglycerol O-Acyltransferase
keywords: DGAT1 inhibitors; Scaffold hopping; Treatment for dyslipidemia