Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France.
Eur J Med Chem. 2012 Oct;56:225-36. doi: 10.1016/j.ejmech.2012.08.029. Epub 2012 Aug 30.
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.
吡咯并[2,3-a]咔唑-3-甲醛是具有体外抗增殖活性的强效 Pim 激酶抑制剂。在本研究中，我们报告了新的 4-取代吡咯并[2,3-a]咔唑的合成和生物学活性（Pim 激酶抑制和体外抗增殖活性）。结果表明，在 3-位没有甲酰基的情况下，在 4-位带有甲氧基羰基的吡咯并[2,3-a]咔唑可以保留对 Pim 激酶的抑制效力（特别是 Pim-3）。此外，发现对 Pim-1 和 Pim-3 激酶具有活性的化合物 27 在微摩尔范围内显示出抗增殖活性。
