1,4,5,6-tetrahydropyrrolo[3,4-c] pyrazoles:: Identification of a potent aurora kinase inhibitor with a favorable antitumor kinase inhibition profile
1,4,5,6-tetrahydropyrrolo[3,4-c] pyrazoles:: Identification of a potent aurora kinase inhibitor with a favorable antitumor kinase inhibition profile
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DOI：
10.1021/jm060897w
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发表时间：
2006-11-30
影响因子：
7.3
通讯作者：
Vianello, Paola
中科院分区：
文献类型：
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作者：
Fancelli, Daniele;Moll, Jurgen;Vianello, Paola
通过对一系列5-苯乙酰基-1，4，5，6-四氢吡咯并[3，4-c]吡唑衍生物抑制Aurora激酶活性的优化，鉴定出化合物9d。这是一种有效的Aurora激酶抑制剂，对其他抗癌激酶靶点也显示出低纳摩尔效力。基于其对不同癌细胞系的高抗增殖活性、有利的化学物理和药代动力学性质以及在体内肿瘤模型中的高功效，最终选择化合物9d用于进一步开发。
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.