Rational design of 4-amino-5,6-diaryl-furo[2,3-d]pyrimidines as potent glycogen synthase kinase-3 inhibitors.
4-Amino-5,6-diaryl-furo[2,3-d]pyrimidines have been identified as inhibitors of glycogen synthase kinase-3beta (GSK-3beta). One representative derivative, 4-amino-3-(4-(benzenesulfonylamino)-phenyl)-2-(3-pyridyl)-furo[2,3-d]pyrimidine (12) exhibited potent GSK-3beta inhibitory activity in low nanomolar level of IC(50). The binding mode was proposed from a docking study.
Miyazaki
Yasushi
Y
GlaxoSmithKline, Tsukuba Research Laboratories, Chemistry Department, 43, Wadai, Tsukuba, Ibaraki 300-4247, Japan.
Maeda
Yutaka
Y
Sato
Hideyuki
H
Nakano
Masato
M
Mellor
Geoffrey W
GW
D015195:Drug Design; D005454:Fluorescence Polarization; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D042787:Receptor, TIE-2 / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3