Sapozhnikova Ksenia A, Slesarchuk Nikita A, Orlov Alexey A, Khvatov Evgeny V, Radchenko Eugene V, Chistov Alexey A, Ustinov Alexey V, Palyulin Vladimir A, Kozlovskaya Liubov I, Osolodkin Dmitry I, Korshun Vladimir A, Brylev Vladimir A
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Miklukho-Maklaya 16/10 Moscow 117997 Russia
Department of Chemistry, Lomonosov Moscow State University Moscow 119991 Russia.
RSC Adv. 2019 Aug 20;9(45):26014-26023. doi: 10.1039/c9ra06313g. eCollection 2019 Aug 19.
The propargylamide of N3-Pom-protected 5-(perylen-3-ylethynyl)uracil acetic acid, a universal precursor, was used in a CuAAC click reaction for the synthesis of several derivatives, including three ramified molecules with high activities against tick-borne encephalitis virus (TBEV). Pentaerythritol-based polyazides were used for the assembly of molecules containing 2⋯4 antiviral 5-(perylen-3-ylethynyl)uracil scaffolds, the first examples of polyvalent perylene antivirals. Cluster compounds showed enhanced absorbance, however, their fluorescence was reduced due to self-quenching. Due to the solubility issues, Pom group removal succeeded only for compounds with one peryleneethynyluracil unit. Four compounds, including one ramified cluster 9f, showed remarkable 1⋯3 nM EC values against TBEV in cell culture.
N3-戊酸甲酯保护的5-(苝-3-基乙炔基)尿嘧啶乙酸的炔丙酰胺作为通用前体，用于铜催化的叠氮化物-炔烃环加成（CuAAC）点击反应，以合成几种衍生物，包括三种对蜱传脑炎病毒（TBEV）具有高活性的分支分子。基于季戊四醇的多叠氮化物用于组装含有2⋯4个抗病毒5-(苝-3-基乙炔基)尿嘧啶支架的分子，这是多价苝类抗病毒药物的首个实例。簇状化合物显示出增强的吸光度，然而，由于自猝灭，它们的荧光减弱。由于溶解性问题，仅对于含有一个苝乙炔基尿嘧啶单元的化合物成功实现了戊酸甲酯基团的去除。四种化合物，包括一种分支簇状化合物9f，在细胞培养中对TBEV显示出显著的1⋯3 nM的半数有效浓度（EC）值。
