title: Pyridine-3-propanoic acids: Discovery of dual PPARalpha/gamma agonists as antidiabetic agents.
abstract: A series of novel pyridine-3-propanoic acids was synthesized. A structure-activity relationship study of these compounds led to the identification of potent dual PPARalpha/gamma agonists with varied isoform selectivity. Based on the results of efficacy studies in diabetic (db/db) mice, and the desired pharmacokinetic parameters, compounds (S)-14 and (S)-19 were selected for further profiling.
authors.affiliation: Department of Diabetes Chemistry, Pfizer Global R&D, 10770 Science Center Drive, San Diego, CA 92121, USA. paul.humphries@pfizer.com <paul.humphries@pfizer.com>
authors.forename: Paul S
authors.initials: PS
authors.lastname: Humphries
authors.forename: Simon
authors.initials: S
authors.lastname: Bailey
authors.forename: Jonathon V
authors.initials: JV
authors.lastname: Almaden
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Barnum
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carlson
authors.forename: Lance C
authors.initials: LC
authors.lastname: Christie
authors.forename: Quyen-Quyen T
authors.initials: QQ
authors.lastname: Do
authors.forename: James D
authors.initials: JD
authors.lastname: Fraser
authors.forename: Mary
authors.initials: M
authors.lastname: Hess
authors.forename: Jack
authors.initials: J
authors.lastname: Kellum
authors.forename: Young H
authors.initials: YH
authors.lastname: Kim
authors.forename: Guy A
authors.initials: GA
authors.lastname: McClellan
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Ogilvie
authors.forename: Brett H
authors.initials: BH
authors.lastname: Simmons
authors.forename: Donald
authors.initials: D
authors.lastname: Skalitzky
authors.forename: Shaoxian
authors.initials: S
authors.lastname: Sun
authors.forename: David
authors.initials: D
authors.lastname: Wilhite
authors.forename: Luke R
authors.initials: LR
authors.lastname: Zehnder
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D004986:Ether / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D011725:Pyridines / Q000097:blood* / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D011725:Pyridines; D045162:Thiazolidinediones; C500090:thiazolidine-2,4-dione; D004986:Ether; C023666:pyridine