Design and Synthesis of Arene Tetra Sulfonate Sodium Salts as Anti-Noroviral Agents

• Main Author: 楊士奇
• Other Authors: 胡紀如
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/20372501602813812002

碩士 === 國立清華大學 === 化學系 === 101 === Norovirus is a category of small non-enveloped and single-stranded RNA viruses from Caliciviridae family, that virus is a major cause of epidemics of acute nonbacterial gastroenteritis in the world. Approximately 50% of all gastroenteritis outbreaks have been reported to be caused by norovirus in the United States. Although outbreaks of norovirus infection often occur in the world, but there is no specific medicine to treat people with norovirus illness. There is thus an unmet need for potent antiviral compounds. Prof. Bolognesi at the university of Milano found two high-potency norovirus inhibitors: Suramin and 8,8'-[carbonylbis(imino-3,1-phenylenecarbonylimino)]bis- 1,3,5-naphthalene-trisulphonic¬ acid hexasodium salt (NF023), thus we cooperate with his team and focus on NF023, that we hope to improve the activity by synthesizing structural analogs of NF023 as anti-norovirus agents. We successfully synthesized three new conjugate compounds containing urea linker by using triphosgene under the condition of adjusted pH value, and confirmed the struture by 1H-NMR, 13C-NMR and high resolution mass spectrometry. From water solubility experiment and partition coefficient data, we can conclude we increase drug lipophilicity successfully compared with NF023 and Suramin.