Synthesis and biological activities of 4-substituted pyrrolo[2,3-a]carbazole Pim kinase inhibitors

被引：26
|
作者：
Giraud, Francis [1 ,2 ]
Akue-Gedu, Rufine [1 ,2 ]
Nauton, Lionel [1 ,2 ]
Candelon, Nicolas [1 ,2 ]
Debiton, Eric [3 ,4 ]
Thery, Vincent [1 ,2 ]
Anizon, Fabrice [1 ,2 ]
Moreau, Pascale [1 ,2 ]
机构：
[1] Univ Blaise Pascal, Clermont Univ, Inst Chim Clermont Ferrand, F-63000 Clermont Ferrand, France
[2] ICCF, CNRS, UMR 6296, F-63171 Aubiere, France
[3] Univ Auvergne, Clermont Univ, F-63000 Clermont Ferrand, France
[4] IMTV, INSERM, UMR 990, F-63005 Clermont Ferrand, France
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 56卷
关键词：
Pyrrolo[2,3-a]carbazole; Suzuki coupling; Photo-induced cyclization; Pim kinase inhibition; In vitro antiproliferative activities; HALIDES; SYSTEM;
D O I：
10.1016/j.ejmech.2012.08.029
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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 and biological activities (Pim kinase inhibition and in vitro antiproliferative potency) of new 4-substituted pyrrolo[2,3-a]carbazoles. The results demonstrated that the Pim kinase inhibitory potency (especially Pim-3) can be conserved for pyrrolo [2,3-a]carbazoles bearing a methoxycarbonyl group at the 4-position without a formyl at the 3-position. Moreover, compound 27 that was found to be active against Pim-1 and Pim-3 kinases showed antiproliferative activities in the micromolar range. (C) 2012 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：225 / 236
页数：12
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