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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.

SUBMITTER: Kohn TJ

PROVIDER: S-EPMC4948010 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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5-Alkyl-2-urea-Substituted Pyridines: Identification of Efficacious Glucokinase Activators with Improved Properties.

Kohn Todd J TJ Du Xiaohui X Lai SuJen S Xiong YuMei Y Komorowski Renee R Veniant Murielle M Fu Zice Z Jiao Xianyun X Pattaropong Vatee V Chow David D Cardozo Mario M Jin Lixia L Conn Marion M DeWolf Walter E WE Kraser Christopher F CF Hinklin Ronald J RJ Boys Mark L ML Medina Julio C JC Houze Jonathan J Dransfield Paul P Coward Peter P

ACS medicinal chemistry letters 20160601 7

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. ...[more]

PMID: 27437074

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