化学
体内
赫尔格
药理学
神经氨酸酶抑制剂
奥司他韦
体外
苯并恶唑
四唑
结构-活动关系
甲型流感病毒
哌嗪
铅化合物
立体化学
病毒
生物化学
病毒学
2019年冠状病毒病(COVID-19)
生物
钾通道
有机化学
生物技术
传染病(医学专业)
病理
疾病
医学
生物物理学
作者
Wenhao Wu,Haiyan Yan,Bolun Jiang,Aoyu Wang,Xingqiong Li,Yuehao Zhang,Jizhou Wu,Xijun Zhong,Rongmei Gao,Apeng Wang,Kai Lv,Yuhuan Li,Mingliang Liu
标识
DOI:10.1016/j.ejmech.2022.114906
摘要
We have already reported the modification on the piperazine and phenyl rings of JNJ4796, a small-molecule fuse inhibitor targeting hemagglutinin (HA). In this study, we described the structure-activity relationship of the benzoxazole and tetrazole rings of JNJ4796. Many derivatives demonstrated good in vitro activity against IAV H1N1and Oseltamivir-resistant IAV H1N1 stains. Although compounds (R)-1e and (R)-1h exhibited excellent in vitro activity, high drug exposure level and low hERG inhibition, they displayed low oral efficacy. Excitedly, (R)-1a, a representative identified in our previous study, was found to show potent in vivo anti-IAV activity with the survival rates of 100%, 100% and 70% at 15, 5 and 1.67 mg/kg, respectively, comparable to JNJ4796. Currently, we are exploring different ways to ease its gastrointestinal response.
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