title: Benzodipyrazoles: a new class of potent CDK2 inhibitors.
abstract: 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.
authors.affiliation: Chemistry Department, Nerviano Medical Sciences, Oncology Business Unit, Viale Pasteur 10, 20014 Nerviano (MI), Italy. roberto.dalessio@nervianoms.com
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Alessio
authors.forename: Alberto
authors.initials: A
authors.lastname: Bargiotti
authors.forename: Suzanne
authors.initials: S
authors.lastname: Metz
authors.forename: M Gabriella
authors.initials: MG
authors.lastname: Brasca
authors.forename: Alexander
authors.initials: A
authors.lastname: Cameron
authors.forename: Antonella
authors.initials: A
authors.lastname: Ermoli
authors.forename: Aurelio
authors.initials: A
authors.lastname: Marsiglio
authors.forename: Paolo
authors.initials: P
authors.lastname: Polucci
authors.forename: Fulvia
authors.initials: F
authors.lastname: Roletto
authors.forename: Marcellino
authors.initials: M
authors.lastname: Tibolla
authors.forename: Michael L
authors.initials: ML
authors.lastname: Vazquez
authors.forename: Anna
authors.initials: A
authors.lastname: Vulpetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Pevarello
mesh_terms: 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
chemical_list: 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