Cdc7 kinase inhibitors

Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships

Ermes Vanotti, Raffaella Amici, Alberto Bargiotti, Jens Berthelsen, Roberta Bosotti, Antonella Ciavolella, Alessandra Cirla, Cinzia Cristiani, Roberto D'Alessio, Barbara Forte, Antonella Isacchi, Katia Martina, Maria Menichincheri, Antonio Molinari, Alessia Montagnoli, Paolo Orsini, Antonio Pillan, Fulvia Roletto, Alessandra Scolaro, Marcellino Tibolla & 4 others Barbara Valsasina, Mario Varasi, Daniele Volpi, Corrado Santocanale

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)487-501
Number of pages15
JournalJournal of Medicinal Chemistry
Volume51
Issue number3
DOIs
Publication statusPublished - Feb 14 2008

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Structure-Activity Relationship
Antineoplastic Agents
Phosphotransferases
Cell death
DNA Replication
Scaffolds
Tumors
Neoplasms
Cell Death
Molecules
DNA
Proteins

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Vanotti, E., Amici, R., Bargiotti, A., Berthelsen, J., Bosotti, R., Ciavolella, A., ... Santocanale, C. (2008). Cdc7 kinase inhibitors: Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships. Journal of Medicinal Chemistry, 51(3), 487-501. https://doi.org/10.1021/jm700956r

Cdc7 kinase inhibitors : Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships. / Vanotti, Ermes; Amici, Raffaella; Bargiotti, Alberto; Berthelsen, Jens; Bosotti, Roberta; Ciavolella, Antonella; Cirla, Alessandra; Cristiani, Cinzia; D'Alessio, Roberto; Forte, Barbara; Isacchi, Antonella; Martina, Katia; Menichincheri, Maria; Molinari, Antonio; Montagnoli, Alessia; Orsini, Paolo; Pillan, Antonio; Roletto, Fulvia; Scolaro, Alessandra; Tibolla, Marcellino; Valsasina, Barbara; Varasi, Mario; Volpi, Daniele; Santocanale, Corrado.

In: Journal of Medicinal Chemistry, Vol. 51, No. 3, 14.02.2008, p. 487-501.

Research output: Contribution to journalArticle

Vanotti, E, Amici, R, Bargiotti, A, Berthelsen, J, Bosotti, R, Ciavolella, A, Cirla, A, Cristiani, C, D'Alessio, R, Forte, B, Isacchi, A, Martina, K, Menichincheri, M, Molinari, A, Montagnoli, A, Orsini, P, Pillan, A, Roletto, F, Scolaro, A, Tibolla, M, Valsasina, B, Varasi, M, Volpi, D & Santocanale, C 2008, 'Cdc7 kinase inhibitors: Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships', Journal of Medicinal Chemistry, vol. 51, no. 3, pp. 487-501. https://doi.org/10.1021/jm700956r
Vanotti, Ermes ; Amici, Raffaella ; Bargiotti, Alberto ; Berthelsen, Jens ; Bosotti, Roberta ; Ciavolella, Antonella ; Cirla, Alessandra ; Cristiani, Cinzia ; D'Alessio, Roberto ; Forte, Barbara ; Isacchi, Antonella ; Martina, Katia ; Menichincheri, Maria ; Molinari, Antonio ; Montagnoli, Alessia ; Orsini, Paolo ; Pillan, Antonio ; Roletto, Fulvia ; Scolaro, Alessandra ; Tibolla, Marcellino ; Valsasina, Barbara ; Varasi, Mario ; Volpi, Daniele ; Santocanale, Corrado. / Cdc7 kinase inhibitors : Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 3. pp. 487-501.
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AU - Vanotti, Ermes

AU - Amici, Raffaella

AU - Bargiotti, Alberto

AU - Berthelsen, Jens

AU - Bosotti, Roberta

AU - Ciavolella, Antonella

AU - Cirla, Alessandra

AU - Cristiani, Cinzia

AU - D'Alessio, Roberto

AU - Forte, Barbara

AU - Isacchi, Antonella

AU - Martina, Katia

AU - Menichincheri, Maria

AU - Molinari, Antonio

AU - Montagnoli, Alessia

AU - Orsini, Paolo

AU - Pillan, Antonio

AU - Roletto, Fulvia

AU - Scolaro, Alessandra

AU - Tibolla, Marcellino

AU - Valsasina, Barbara

AU - Varasi, Mario

AU - Volpi, Daniele

AU - Santocanale, Corrado

PY - 2008/2/14

Y1 - 2008/2/14

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