6-substituted pyrrolo[3,4-c]pyrazoles: An improved class of CDK2 inhibitors

被引：23

作者：

Brasca, Maria Gabriella

Albanese, Clara

Amici, Raffaella

Ballinari, Dario

Corti, Luca

Croci, Valter

Fancelli, Daniele

Fiorentini, Francesco

Nesi, Marcella

Orsini, Paolo

Orzi, Fabrizio

Pastori, Wilma

Perrone, Ettore

Pesenti, Enrico

Pevarello, Paolo

Riccardi-Sirtori, Federico

Roletto, Fulvia

Roussel, Patrick

Varasi, Mario

Vulpetti, Anna

Mercurio, Ciro

机构：

[1] Oncology Business Unit, Department of Chemistry, Nerviano Medical Sciences, 20014 Nerviano MI

[2] Oncology Business Unit, Department of Biology, Nerviano Medical Sciences, 20014 Nerviano MI

[3] Preclinical Development, Nerviano Medical Sciences, 20014 Nerviano MI

来源：

CHEMMEDCHEM | 2007年 / 2卷 / 06期

关键词：

MULTISTEP ORGANIC-SYNTHESIS; SOLID-SUPPORTED REAGENTS; 3-AMINOPYRAZOLE INHIBITORS; KINASE INHIBITION; ANTITUMOR AGENTS; CELL-CYCLE; POTENT; PHASE; TRANSITION; ROLES;

D O I：

10.1002/cmdc.200600302

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have recently reported a new class of CDK2/cyclin A inhibitors based on a bicyclic tetrohydropyrrolo[3,4-clpyrazole scaffold. The introduction of small alkyl or cycloalkyl groups in position 6 of this scaffold allowed variation at the other two diversity points. Conventional and polymer-assisted solution phase chemistry provided a way of generating compounds with improved biochemicol and cellular activity. Optimization of the physical properties and pharmacokinetic profile led to a compound which exhibited good efficacy in vivo on A2780 human ovarian carcinoma.

引用

页码：841 / 852

页数：12

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