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 TibollaBarbara Valsasina, Mario Varasi, Daniele Volpi, Corrado Santocanale

Research output: Contribution to journalArticle

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

    Fingerprint

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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., ... 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