Design and synthesis of 7-hydroxy-1H-benzoimidazole derivatives as novel inhibitors of glycogen synthase kinase-3beta.
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.
Shin
Dongkyu
D
CrystalGenomics, Inc., Asan Institute for Life Sciences, 388-1 Pungnap-2dong, Songpa-gu, Seoul 138-736, Republic of Korea.
Lee
Seung-Chul
SC
Heo
Yong-Seok
YS
Lee
Woon-Young
WY
Cho
Yong-Soon
YS
Kim
Yong Eun
YE
Hyun
Young-Lan
YL
Cho
Joong Myung
JM
Lee
Yoon Sup
YS
Ro
Seonggu
S
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
D007093:Imidazoles; D047428:Protein Kinase Inhibitors; C029899:imidazole; D038362:Glycogen Synthase Kinase 3; D001554:Benzene