Benzodipyrazoles: a new class of potent CDK2 inhibitors.
The synthesis and the preliminary expansion of this new class of CDK2 inhibitors are presented. The synthesis was accomplished using a solution-phase protocol amenable to rapid parallel expansion and suitable to be scaled-up in view of possible lead development. Following a medicinal chemistry program aimed at improving cell permeability and selectivity, a series of compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit tumor cell proliferation has been obtained.
D'Alessio
Roberto
R
Chemistry Department, Nerviano Medical Sciences, Oncology Business Unit, Viale Pasteur 10, 20014 Nerviano (MI), Italy. roberto.dalessio@nervianoms.com
Bargiotti
Alberto
A
Metz
Suzanne
S
Brasca
M Gabriella
MG
Cameron
Alexander
A
Ermoli
Antonella
A
Marsiglio
Aurelio
A
Polucci
Paolo
P
Roletto
Fulvia
F
Tibolla
Marcellino
M
Vazquez
Michael L
ML
Vulpetti
Anna
A
Pevarello
Paolo
P
D042846:CDC2-CDC28 Kinases / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003460:Crystallization; D018360:Crystallography, X-Ray; D019925:Cyclin A / Q000037:antagonists & inhibitors; D051357:Cyclin-Dependent Kinase 2; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000145:classification* / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000145:classification* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D019925:Cyclin A; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D038362:Glycogen Synthase Kinase 3