Research Centre of Modern Analytical Technology, Tianjin University of Science & Technology, No. 29, 13th Avenue, TEDA, Tianjin, 300457, China.
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, Tianjin, 300457, China.
Carbohydr Res. 2019 May 15;477:32-38. doi: 10.1016/j.carres.2019.03.012. Epub 2019 Apr 1.
A panel of divalent oseltamivir and guanidino oseltamivir analogues with esterification on the carboxyl acid group as potent inhibitors of influenza virus neuraminidase was prepared via click reaction. The primary structure activity relationship study demonstrated that appropriate distance between two oseltamivir monomers around 30 Å can crosslink two adjacent neuraminidase tetramers on the virion surface and result in highly effective NA inhibitors against three strains of influenza virus and H7N9 virus like particle. This strategy also provides a basis for the multivalent modification on oseltamivir.
通过点击反应，制备了一组带有羧酸酯化的二价奥司他韦和胍基奥司他韦类似物作为流感病毒神经氨酸酶的有效抑制剂。初步的结构活性关系研究表明，两个奥司他韦单体之间约 30Å 的适当距离可以交联病毒表面上的两个相邻的神经氨酸酶四聚体，并导致对三种流感病毒株和 H7N9 病毒样颗粒具有高度有效的 NA 抑制剂。该策略还为奥司他韦的多价修饰提供了基础。
