Cell Division Cycle 7 Kinase Inhibitors: 1H-Pyrrolo[2,3-b]pyridines, Synthesis and Structure - Activity Relationships

被引：50

作者：

Ermoli, Antonella ^{[1
]}

Bargiotti, Alberto ^{[1
]}

Brasca, Maria Gabriella ^{[1
]}

Ciavolella, Antonella ^{[1
]}

Colombo, Nicoletta ^{[1
]}

Fachin, Gabriele ^{[1
]}

Isacchi, Antonella ^{[1
]}

Menichincheri, Maria ^{[1
]}

Molinari, Antonio ^{[1
]}

Montagnoli, Alessia ^{[1
]}

Pillan, Antonio ^{[1
]}

Rainoldi, Sonia ^{[1
]}

Sirtori, Federico Riccardi ^{[1
]}

Sola, Francesco ^{[1
]}

Thieffine, Sandrine ^{[1
]}

Tibolla, Marcellino ^{[1
]}

Valsasina, Barbara ^{[1
]}

Volpi, Daniele ^{[1
]}

Santocanale, Corrado ^{[1
]}

Vanotti, Ermes ^{[1
]}

机构：

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 14期

关键词：

ANTITUMOR AGENTS; DNA-REPLICATION; CDC7; PYRROLOPYRIDINONES; INITIATION; REVEALS; PROTEIN; TARGET; POTENT; ASSAY;

D O I：

10.1021/jm900248g

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cdc7 kinase has recently emerged as an attractive target for cancer therapy and low-molecular-weight inhibitors of Cdc7 kinase have been found to be effective in the inhibition of tumor growth in animal models. In this paper, we describe synthesis and structure-activity relationships of new 1H-pyrrolo[2, 3-b]pyridine derivatives identified as inhibitors of Cdc7 kinase. Progress from (Z)-2-phenyl-5-(1H- pyrrolo[2,3-b]pyridin-3-ylmethylene)-3,5-dihydro-4H-imidazol-4-one (1) to [(Z)-2-(benzylamino)-5- (1H-pyrrolo[2,3-b]pyridin-3-ylmethylene)-1,3-thiazol-4(5H)-one] (42), a potent ATP mimetic inhibitor of Cdc7 kinase with IC50 value of 7 nM, is also reported.

引用

页码：4380 / 4390

页数：11

共 36 条

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