title: Design and synthesis of 7-hydroxy-1H-benzoimidazole derivatives as novel inhibitors of glycogen synthase kinase-3beta.
abstract: A hydroxy functional group was introduced as the hydrogen bond donor and acceptor at the hinge region of protein kinase in order to develop novel ATP-competitive inhibitors. Several derivatives of 7-hydroxyl-1H-benzoimidazole were designed as inhibitors of glycogen synthase kinase-3beta with the help of ab initio calculations and a docking study. Enzymatic assay and an X-ray complex study showed that these designed compounds were highly potent ATP-competitive inhibitors.
authors.affiliation: CrystalGenomics, Inc., Asan Institute for Life Sciences, 388-1 Pungnap-2dong, Songpa-gu, Seoul 138-736, Republic of Korea.
authors.forename: Dongkyu
authors.initials: D
authors.lastname: Shin
authors.forename: Seung-Chul
authors.initials: SC
authors.lastname: Lee
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Heo
authors.forename: Woon-Young
authors.initials: WY
authors.lastname: Lee
authors.forename: Yong-Soon
authors.initials: YS
authors.lastname: Cho
authors.forename: Yong Eun
authors.initials: YE
authors.lastname: Kim
authors.forename: Young-Lan
authors.initials: YL
authors.lastname: Hyun
authors.forename: Joong Myung
authors.initials: JM
authors.lastname: Cho
authors.forename: Yoon Sup
authors.initials: YS
authors.lastname: Lee
authors.forename: Seonggu
authors.initials: S
authors.lastname: Ro
mesh_terms: D001554:Benzene / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; C029899:imidazole; D038362:Glycogen Synthase Kinase 3; D001554:Benzene