Anilinopyrazole as selective CDK2 inhibitors: design, synthesis, biological evaluation, and X-ray crystallographic analysis.
A novel series of anilinopyrazoles has been designed based on the X-ray crystal structure analysis. Most compounds from this series not only show sub-nanomolar IC(50) values for CDK2, but also demonstrate almost 1000-fold selectivity to other kinases including CDK1.
Tang
Jun
J
GlaxoSmithKline K. K. Tsukuba Research Laboratories, 43 Wadai Tsukuba, Ibaraki 300-4247, Japan. jt21064@gsk.com
Shewchuk
Lisa M
LM
Sato
Hideyuki
H
Hasegawa
Masaichi
M
Washio
Yoshiaki
Y
Nishigaki
Naohiko
N
D001665:Binding Sites; D042846:CDC2-CDC28 Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D018360:Crystallography, X-Ray; D051357:Cyclin-Dependent Kinase 2; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011485:Protein Binding; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011720:Pyrazoles; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2