title: 5-Alkyl-2-urea-Substituted Pyridines: Identification of Efficacious Glucokinase Activators with Improved Properties.
abstract: Two 1-(4-aryl-5-alkyl-pyridin-2-yl)-3-methylurea glucokinase activators were identified with robust in vivo efficacy. These two compounds possessed higher solubilities than the previously identified triaryl compounds (i.e., AM-2394). Structure-activity relationship studies are presented along with relevant pharmacokinetic and in vivo data.
authors.affiliation: Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Kohn
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Du
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: SuJen
authors.initials: S
authors.lastname: Lai
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: YuMei
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
authors.forename: Renee
authors.initials: R
authors.lastname: Komorowski
authors.affiliation: Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
authors.forename: Murielle
authors.initials: M
authors.lastname: Veniant
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Zice
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Xianyun
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Vatee
authors.initials: V
authors.lastname: Pattaropong
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: David
authors.initials: D
authors.lastname: Chow
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Mario
authors.initials: M
authors.lastname: Cardozo
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Lixia
authors.initials: L
authors.lastname: Jin
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Marion
authors.initials: M
authors.lastname: Conn
authors.affiliation: Array BioPharma Inc. , 3200 Walnut Street, Boulder, Colorado 80301, United States.
authors.forename: Walter E
authors.initials: WE
authors.lastname: DeWolf
authors.affiliation: Array BioPharma Inc. , 3200 Walnut Street, Boulder, Colorado 80301, United States.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Kraser
authors.affiliation: Array BioPharma Inc. , 3200 Walnut Street, Boulder, Colorado 80301, United States.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Hinklin
authors.affiliation: Array BioPharma Inc. , 3200 Walnut Street, Boulder, Colorado 80301, United States.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Boys
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Medina
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Houze
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Dransfield
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Coward
keywords: GKA; Type 2 diabetes; glucokinase activator; methylurea-substituted pyridines