title: Design, synthesis, and in vivo activity of novel inhibitors of delta-5 desaturase for the treatment of metabolic syndrome.
abstract: The synthesis, SAR, and in vivo activity of inhibitors of delta-5 desaturase are described. Ring-constraint of the initial series provided access to a variety of in vitro active chemotypes, from which the indazole was selected. Examples from the indazole series displayed in vivo activity in reducing the enzymatic activity of liver delta-5 desaturase.
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States. Electronic address: simondpbaugh@gmail.com.
authors.forename: Simon D P
authors.initials: SD
authors.lastname: Baugh
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Pabba
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Barbosa
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Coulter
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States.
authors.forename: Urvi
authors.initials: U
authors.lastname: Desai
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Gay
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States.
authors.forename: Suma
authors.initials: S
authors.lastname: Gopinathan
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Han
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States.
authors.forename: Rajee
authors.initials: R
authors.lastname: Hari
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: S David
authors.initials: SD
authors.lastname: Kimball
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Huy V
authors.initials: HV
authors.lastname: Nguyen
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Chi-You
authors.initials: CY
authors.lastname: Ni
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States.
authors.forename: David R
authors.initials: DR
authors.lastname: Powell
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States.
authors.forename: Arian
authors.initials: A
authors.lastname: Smith
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Terranova
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States.
authors.forename: Alan
authors.initials: A
authors.lastname: Wilson
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States.
authors.forename: Xuan-Chuan
authors.initials: XC
authors.lastname: Yu
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Lombardo
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000090943:Delta-5 Fatty Acid Desaturase; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D044943:Fatty Acid Desaturases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000090943:Delta-5 Fatty Acid Desaturase; D004791:Enzyme Inhibitors; D044943:Fatty Acid Desaturases
keywords: Delta-5 desaturase; In vivo efficacy; Indazole; Metabolic syndrome; Ring constraint