title: Discovery of novel quinoline carboxylic acid series as DGAT1 inhibitors.
abstract: Herein we report the design and synthesis of a series of novel bicyclic DGAT1 inhibitors with a carboxylic acid moiety. The optimization of the initial lead compound 7 based on in vitro and in vivo activity led to the discovery of potent indoline and quinoline classes of DGAT1 inhibitors. The structure-activity relationship studies of these novel series of bicyclic carboxylic acid derivatives as DGAT1 inhibitors are described.
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA. Electronic address: gang.zhou@merck.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Ting
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Grant
authors.initials: G
authors.lastname: Wishart
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Zorn
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Aslanian
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Biological Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Smith
authors.affiliation: Department of Biological Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Walker
authors.affiliation: Department of Biological Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: John
authors.initials: J
authors.lastname: Cook
authors.affiliation: Department of Biological Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Van Heek
authors.affiliation: Department of Biological Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Lachowicz
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D015363:Quinolones; C494881:DGAT1 protein, human; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase
keywords: Cyclohexanecarboxylic acid; DGAT1 inhibitor; Diacylglycerol acyltransferase inhibitor; Indoline; Quinoline; Triacylglyceride