title: Cdc7 kinase inhibitors: pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships.
abstract: Cdc7 kinase is an essential protein that promotes DNA replication in eukaryotic organisms. Genetic evidence indicates that Cdc7 inhibition can cause selective tumor-cell death in a p53-independent manner, supporting the rationale for developing Cdc7 small-molecule inhibitors for the treatment of cancers. In this paper, the synthesis and structure-activity relationships of 2-heteroaryl-pyrrolopyridinones, the first potent Cdc7 kinase inhibitors, are described. Starting from 2-pyridin-4-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one, progress toward a simple scaffold, tailored for Cdc7 inhibition, is reported.
authors.affiliation: Nerviano Medical Sciences Srl, Viale Pasteur 10, 20014 Nerviano, Milano, Italy. ermes.vanotti@nervianoms.com
authors.forename: Ermes
authors.initials: E
authors.lastname: Vanotti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Amici
authors.forename: Alberto
authors.initials: A
authors.lastname: Bargiotti
authors.forename: Jens
authors.initials: J
authors.lastname: Berthelsen
authors.forename: Roberta
authors.initials: R
authors.lastname: Bosotti
authors.forename: Antonella
authors.initials: A
authors.lastname: Ciavolella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cirla
authors.forename: Cinzia
authors.initials: C
authors.lastname: Cristiani
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Alessio
authors.forename: Barbara
authors.initials: B
authors.lastname: Forte
authors.forename: Antonella
authors.initials: A
authors.lastname: Isacchi
authors.forename: Katia
authors.initials: K
authors.lastname: Martina
authors.forename: Maria
authors.initials: M
authors.lastname: Menichincheri
authors.forename: Antonio
authors.initials: A
authors.lastname: Molinari
authors.forename: Alessia
authors.initials: A
authors.lastname: Montagnoli
authors.forename: Paolo
authors.initials: P
authors.lastname: Orsini
authors.forename: Antonio
authors.initials: A
authors.lastname: Pillan
authors.forename: Fulvia
authors.initials: F
authors.lastname: Roletto
authors.forename: Alessandra
authors.initials: A
authors.lastname: Scolaro
authors.forename: Marcellino
authors.initials: M
authors.lastname: Tibolla
authors.forename: Barbara
authors.initials: B
authors.lastname: Valsasina
authors.forename: Mario
authors.initials: M
authors.lastname: Varasi
authors.forename: Daniele
authors.initials: D
authors.lastname: Volpi
authors.forename: Corrado
authors.initials: C
authors.lastname: Santocanale
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D005663:Furans; D011728:Pyridones; D011758:Pyrroles; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases