title: 3-Amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: a new class of CDK2 inhibitors.
abstract: We have recently reported about a new class of Aurora-A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. Here we describe the synthesis and early expansion of CDK2/cyclin A-E inhibitors belonging to the same chemical class. Synthesis of the compounds was accomplished using a solution-phase protocol amenable to rapid parallel expansion. Compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit CDK2-mediated tumor cell proliferation have been obtained.
authors.affiliation: Department of Chemistry, Nerviano Medical Science, BU-Oncology, Via Pasteur 10, 20014 Nerviano MI, Italy. paolo.pevarello@nervianoms.com
authors.forename: Paolo
authors.initials: P
authors.lastname: Pevarello
authors.forename: Daniele
authors.initials: D
authors.lastname: Fancelli
authors.forename: Anna
authors.initials: A
authors.lastname: Vulpetti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Amici
authors.forename: Manuela
authors.initials: M
authors.lastname: Villa
authors.forename: Valeria
authors.initials: V
authors.lastname: Pittalà
authors.forename: Paola
authors.initials: P
authors.lastname: Vianello
authors.forename: Alexander
authors.initials: A
authors.lastname: Cameron
authors.forename: Marina
authors.initials: M
authors.lastname: Ciomei
authors.forename: Ciro
authors.initials: C
authors.lastname: Mercurio
authors.forename: James R
authors.initials: JR
authors.lastname: Bischoff
authors.forename: Fulvia
authors.initials: F
authors.lastname: Roletto
authors.forename: Mario
authors.initials: M
authors.lastname: Varasi
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Brasca
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology*; D064127:Aurora Kinases; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D019925:Cyclin A / Q000037:antagonists & inhibitors; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D019925:Cyclin A; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2