2. Academic Validation
  3. Cdc7 kinase inhibitors: pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships

Cdc7 kinase inhibitors: pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships

  • J Med Chem. 2008 Feb 14;51(3):487-501. doi: 10.1021/jm700956r.
Ermes Vanotti 1,  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,  Barbara Valsasina,  Mario Varasi,  Daniele Volpi,  Corrado Santocanale
Affiliations

Affiliation

  • 1 Nerviano Medical Sciences Srl, Viale Pasteur 10, 20014 Nerviano, Milano, Italy. ermes.vanotti@nervianoms.com
PMID: 18201066 DOI: 10.1021/jm700956r
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.

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