4-Acylamino-6-arylfuro[2,3-d]pyrimidines: potent and selective glycogen synthase kinase-3 inhibitors.
Modeling studies of a furo[2,3-d]pyrimidine GSK-3 hit compound 1 superimposed onto the X-ray crystal structure of a legacy pyrazolo[3,4-c]pyridazine GSK-3 inhibitor 2 led to the identification of 4-acylamino-6-arylfuro[2,3-d]pyrimidine template 3. Synthesis of analogues based on template 3 has resulted in a number of potent and selective GSK-3beta inhibitors. The most potent and selective compound was the m-pyridyl analogue 24.
Maeda
Yutaka
Y
Chemistry Department, Tsukuba Research Laboratories, GlaxoSmithKline K.K., Wadai 43, Tsukuba, Ibaraki 300-4247, Japan.
Nakano
Masato
M
Sato
Hideyuki
H
Miyazaki
Yasushi
Y
Schweiker
Stephanie L
SL
Smith
Jeffery L
JL
Truesdale
Anne T
AT
D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D011743:Pyrimidines; D040301:Vascular Endothelial Growth Factor Receptor-2; D038362:Glycogen Synthase Kinase 3