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

被引:49
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
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
收藏
页码:4380 / 4390
页数:11
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