基于吲哚和多组分反应的大环化合物作为p53-MDM2拮抗剂的设计
Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists.
作者信息
Neochoritis Constantinos G, Kazemi Miraki Maryam, Abdelraheem Eman M M, Surmiak Ewa, Zarganes-Tzitzikas Tryfon, Łabuzek Beata, Holak Tad A, Dömling Alexander
机构信息
Department of Drug Design, University of Groningen, Antonius Deusinglaan 1, 9700 AD Groningen, The Netherlands.
Chemistry Department, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran.
出版信息
Beilstein J Org Chem. 2019 Feb 20;15:513-520. doi: 10.3762/bjoc.15.45. eCollection 2019.
Macrocycles were designed to antagonize the protein-protein interaction p53-MDM2 based on the three-finger pharmacophore FWL. The synthesis was accomplished by a rapid, one-pot synthesis of indole-based macrocycles based on Ugi macrocyclization. The reaction of 12 different α,ω-amino acids and different indole-3-carboxaldehyde derivatives afforded a unique library of macrocycles otherwise difficult to access. Screening of the library for p53-MDM2 inhibition by fluorescence polarization and H,N HSQC NMR measurements confirm MDM2 binding.
基于三指药效团FWL设计了大环化合物以拮抗蛋白质-蛋白质相互作用p53-MDM2。通过基于Ugi大环化反应的快速一锅法合成吲哚基大环化合物来完成合成。12种不同的α,ω-氨基酸与不同的吲哚-3-甲醛衍生物反应，得到了一个独特的大环化合物库，否则难以获得。通过荧光偏振和H,N HSQC NMR测量筛选该库对p53-MDM2的抑制作用，证实了MDM2的结合。
Zotero 插件