Université de Reims-Champagne-Ardenne, Institut de Chimie Moléculaire de Reims, CNRS UMR 6229, Groupe BSMA, UFR de Pharmacie, 51 rue Cognacq-Jay, F-51096 Reims, Cedex, France.
Org Biomol Chem. 2010 Oct 21;8(20):4625-36. doi: 10.1039/c0ob00149j. Epub 2010 Aug 24.
A short route, involving a tetramolecular condensation reaction and a Pd/C catalyst-H(2)-mediated reductive N-heteroannulation as the key-steps, has been found for the synthesis of some new penta- and heptacyclic indolo- (12), quinolino- (13) and indoloquinolinocarbazole (11) derivatives. HF-DFT (B3LYP) energy profiles and NMR calculations were carried out to help in the understanding of the experimental results. N-Alkylated indoloquinolinocarbazoles (16b, 17a, 17b and 18) were prepared and screened essentially toward some cancer-(G-quadruplex, DNA, topoisomerase I) and CNS-related (kinases) targets. Biological results evidenced 13 as a potent CDK-5 and GSK-3β kinases inhibitor, while di- or triaminopropyl-substituted indoloquinolinocarbazoles 17b or 18 targeted rather DNA-duplex or telomeric G-quadruplex structures, respectively.
发现了一条短路线，涉及四分子缩合反应和 Pd/C 催化剂-H(2)-介导的还原 N-杂环加成作为关键步骤，用于合成一些新的五元和七元吲哚-(12)、喹啉-(13)和吲哚喹啉咔唑(11)衍生物。进行了 HF-DFT(B3LYP)能量剖面和 NMR 计算，以帮助理解实验结果。N-烷基化吲哚喹啉咔唑(16b、17a、17b 和 18)被制备并进行了基本筛选，针对一些癌症-(G-四链体、DNA、拓扑异构酶 I)和中枢神经系统相关(激酶)靶标。生物学结果表明 13 是一种有效的 CDK-5 和 GSK-3β 激酶抑制剂，而二氨基或三氨基丙基取代的吲哚喹啉咔唑 17b 或 18 分别靶向 DNA-双链或端粒 G-四链体结构。
