Use of copper(I) catalyzed azide alkyne cycloaddition (CuAAC) for the preparation of conjugated pyrrolo[2,3-a]carbazole Pim kinase inhibitors

被引：23

作者：

Letribot, Boris ^{[1
,2
]}

Akue-Gedu, Rufine ^{[1
,2
]}

Santio, Niina M. ^{[3
,4
,5
]}

El-Ghozzi, Malika ^{[1
,2
]}

Avignant, Daniel ^{[1
,2
]}

Cisnetti, Federico ^{[1
,2
]}

Koskinen, Paivi J. ^{[3
,4
,5
]}

Gautier, Arnaud ^{[1
,2
]}

Anizon, Fabrice ^{[1
,2
]}

Moreau, Pascale ^{[1
,2
]}

机构：

[1] ICCF, CNRS, UMR 6296, F-63171 Aubiere, France

[2] Univ Blaise Pascal, Clermont Univ, Inst Chim Clermont Ferrand, F-63000 Clermont Ferrand, France

[3] Univ Turku, Turku Ctr Biotechnol, SF-20500 Turku, Finland

[4] Abo Akad Univ, Turku, Finland

[5] Univ Turku, Dept Biol, SF-20500 Turku, Finland

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 50卷

基金：

芬兰科学院;

关键词：

Pyrrolo[2,3-a]carbazole-3-carbaldehyde; Pim kinase inhibition; CuAAC (Copper(I) Catalyzed Azide Alkyne Cycloaddition);

D O I：

10.1016/j.ejmech.2012.02.009

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

We have previously demonstrated that pyrrolo[2,3-a]carbazole-3-carbaldehydes are potent Pim kinase inhibitors with in vitro antiproliferative activities. In the present study, we report the synthesis of new pyrrolocarbazoles substituted at the N-10 position. When their ability to inhibit Pim kinase activities were evaluated in in vitro assays, we observed that this nitrogen atom can be substituted without loss of Pim-1 and Pim-3 inhibitory potencies. Moreover, when we added a fluorescent dansyl group (compound 13), we were able to show that 13 penetrates the plasma membrane and enters the cytoplasm. (C) 2012 Elsevier Masson SAS. All rights reserved.

引用

页码：304 / 310

页数：7

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