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

被引：85

作者：

Vanotti, Ermes ^{[1
]}

Amici, Raffaella ^{[1
]}

Bargiotti, Alberto ^{[1
]}

Berthelsen, Jens ^{[1
]}

Bosotti, Roberta ^{[1
]}

Ciavolella, Antonella ^{[1
]}

Cirla, Alessandra ^{[1
]}

Cristiani, Cinzia ^{[1
]}

D'Alessio, Roberto ^{[1
]}

Forte, Barbara ^{[1
]}

Isacchi, Antonella ^{[1
]}

Martina, Katia ^{[1
]}

Menichincheri, Maria ^{[1
]}

Molinari, Antonio ^{[1
]}

Montagnoli, Alessia ^{[1
]}

Orsini, Paolo ^{[1
]}

Pillan, Antonio ^{[1
]}

Roletto, Fulvia ^{[1
]}

Scolaro, Alessandra ^{[1
]}

Tibolla, Marcellino ^{[1
]}

Valsasina, Barbara ^{[1
]}

Varasi, Mario ^{[1
]}

Volpi, Daniele ^{[1
]}

Santocanale, Corrado ^{[1
]}

机构：

[1] Nerviano Med Sci Srl, I-20014 Milan, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 03期

关键词：

D O I：

10.1021/jm700956r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：487 / 501

页数：15

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