1,4,5,6-tetrahydropyrrolo[3,4-c] pyrazoles:: Identification of a potent aurora kinase inhibitor with a favorable antitumor kinase inhibition profile

被引：181

作者：

Fancelli, Daniele ^{[1
]}

Moll, Jurgen ^{[1
]}

Varasi, Mario ^{[1
]}

Bravo, Rodrigo ^{[1
]}

Artico, Roberta ^{[1
]}

Berta, Daniela ^{[1
]}

Bindi, Simona ^{[1
]}

Cameron, Alexander ^{[1
]}

Candiani, Ilaria ^{[1
]}

Cappella, Paolo ^{[1
]}

Carpinelli, Patrizia ^{[1
]}

Croci, Walter ^{[1
]}

Forte, Barbara ^{[1
]}

Giorgini, Maria Laura ^{[1
]}

Klapwijk, Jan ^{[1
]}

Marsiglio, Aurelio ^{[1
]}

Pesenti, Enrico ^{[1
]}

Rocchetti, Maurizio ^{[1
]}

Roletto, Fulvia ^{[1
]}

Severino, Dino ^{[1
]}

Soncini, Chiara ^{[1
]}

Storici, Paola ^{[1
]}

Tonani, Roberto ^{[1
]}

Zugnoni, Paola ^{[1
]}

Vianello, Paola ^{[1
]}

机构：

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 24期

关键词：

D O I：

10.1021/jm060897w

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c] pyrazole derivatives toward the inhibition of Aurora kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora kinases that also shows low nanomolar potency against additional anticancer kinase targets. Based on its high antiproliferative activity on different cancer cell lines, favorable chemico-physical and pharmacokinetic properties, and high efficacy in in vivo tumor models, compound 9d was ultimately selected for further development.

引用

页码：7247 / 7251

页数：5

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