title: Synthesis and evaluation of 8-amino-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one derivatives as glycogen synthase kinase-3 (GSK-3) inhibitors.
abstract: New potent glycogen synthase kinase-3 (GSK-3) inhibitors, 8-amino-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one derivatives, were designed by modeling, synthesized and evaluated in vitro. Compound 17c showed good potency in enzyme and cell-based assays (IC50=111 nM, EC50=1.78 μM). Moreover, it has demonstrated desirable water solubility, PK profile, and moderate brain penetration.
authors.affiliation: Division of New Drug Development, R&D Center, Jeil Pharmaceutical Co., Ltd. 117-1, Keungok-Ri, Baekam-Myun, Cheoin-Gu, Yongin-City, Kyunggi-Do 449-861, Republic of Korea.
authors.forename: Kwangwoo
authors.initials: K
authors.lastname: Chun
authors.forename: Ji-Seon
authors.initials: JS
authors.lastname: Park
authors.forename: Han-Chang
authors.initials: HC
authors.lastname: Lee
authors.forename: Young-Ha
authors.initials: YH
authors.lastname: Kim
authors.forename: In-Hea
authors.initials: IH
authors.lastname: Ye
authors.forename: Kang-Jeon
authors.initials: KJ
authors.lastname: Kim
authors.forename: Il-Whea
authors.initials: IW
authors.lastname: Ku
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Noh
authors.forename: Goang-Won
authors.initials: GW
authors.lastname: Cho
authors.forename: Heejaung
authors.initials: H
authors.lastname: Kim
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Kim
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011994:Recombinant Proteins; D014230:Triazoles; D038362:Glycogen Synthase Kinase 3