36244-64-1Relevant academic research and scientific papers
5-Hydroxyindole-based EZH2 inhibitors assembled via TCCA-catalyzed condensation and Nenitzescu reactions
Chen, Guoliang,Du, Fangyu,Sun, Wenjiao,Wang, Lihui,Wu, Chunfu,Yang, Cheng,Zhou, Qifan
, (2020)
5-Hydroxyindole derivatives have various demonstrated biological activities. Herein, we used 5-hydroxyindole as a synthetic starting point for structural alterations in a combinatorial process to synthesize 22 different compounds with EZH2 inhibitor pharmacophores. A series of 5-hydroxyindole-derived compounds were screened inhibitory activities against K562 cells. According to molecular modeling and in vitro biological activity assays, the preliminary structure-activity relationship was summarized. Compound L–04 improved both the H3K27Me3 reduction and antiproliferation parameters (IC50 = 52.6 μM). These findings revealed that compound L–04 is worthy of consideration as a lead compound to design more potent EZH2 inhibitors. During the preparation of compounds, we discovered that trichloroisocyanuric acid (TCCA) is a novel catalyst which demonstrates condensation-promoting effects. To gain insight into the reaction, in situ React IR technology was used to confirm the reactivity. Different amines were condensed in high yields with β-diketones or β-ketoesters in the presence of TCCA to afford the corresponding products in a short time (10~20 min), which displayed some advantages and provided an alternative condensation strategy.
Sequential activation of σ-bonds: Intermolecular cascade annulation with migration and remote functionalization
Dhara, Dipankar,Sengupta, Tista,Khamarui, Saikat,Ghosh, Sukla,Maiti, Dilip K.
, p. 1663 - 1673 (2014/01/17)
We demonstrate a new catalytic property of the lanthanide compound CeCl3.7H2O which sequentially activates N-H, sp 2 C-H and sp3 C-H σ-bonds at ambient temperature. The powerful catalyst enables selective C-C and C-N bond-forming intermolecular cascade annulation between enamines and diaryl-1,2-diketone to afford functionalized 3,3-diaryl-3-pyrrolin-2-ones involving migration of an aromatic ring. We have also initiated a new multicomponent strategy utilizing readily available and inexpensive precursors and environmentally benign CeCl 3.7H2O as an efficient catalyst under benign reaction conditions towards direct synthesis of several N-heterocycles including pentasubstituted 2-pyrrolinones and pyrroles. These observations provide new prospects and perspectives in σ-bond activation process for easy access to functional molecules.
