title: 6-Substituted pyrrolo[3,4-c]pyrazoles: an improved class of CDK2 inhibitors.
abstract: We have recently reported a new class of CDK2/cyclin A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. The introduction of small alkyl or cycloalkyl groups in position 6 of this scaffold allowed variation at the other two diversity points. Conventional and polymer-assisted solution phase chemistry provided a way of generating compounds with improved biochemical and cellular activity. Optimization of the physical properties and pharmacokinetic profile led to a compound which exhibited good efficacy in vivo on A2780 human ovarian carcinoma.
authors: Oncology Business Unit, Department of Chemistry, Nerviano Medical Sciences, Viale Pasteur 10, 20014 Nerviano MI, Italy. gabriella.brasca@nervianoms.com
authors: Maria Gabriella
authors: MG
authors: Brasca
authors: Clara
authors: C
authors: Albanese
authors: Raffaella
authors: R
authors: Amici
authors: Dario
authors: D
authors: Ballinari
authors: Luca
authors: L
authors: Corti
authors: Valter
authors: V
authors: Croci
authors: Daniele
authors: D
authors: Fancelli
authors: Francesco
authors: F
authors: Fiorentini
authors: Marcella
authors: M
authors: Nesi
authors: Paolo
authors: P
authors: Orsini
authors: Fabrizio
authors: F
authors: Orzi
authors: Wilma
authors: W
authors: Pastori
authors: Ettore
authors: E
authors: Perrone
authors: Enrico
authors: E
authors: Pesenti
authors: Paolo
authors: P
authors: Pevarello
authors: Federico
authors: F
authors: Riccardi-Sirtori
authors: Fulvia
authors: F
authors: Roletto
authors: Patrick
authors: P
authors: Roussel
authors: Mario
authors: M
authors: Varasi
authors: Anna
authors: A
authors: Vulpetti
authors: Ciro
authors: C
authors: Mercurio
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000145:classification / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000145:classification / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000145:classification* / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006131:Growth Inhibitors; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011758:Pyrroles; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2