Design and Synthesis of SARS-CoV Protease Inhibitors: Small Libraries of a-Hydroxy Diethyl Phosphonate, a-Hydroxy Amide and a-Keto Amide
Date Issued
2004
Date
2004
Author(s)
Huang, Hung-Jyun
DOI
zh-TW
Abstract
Severe Acute Respiratory Syndrome (SARS) is caused by infection with a novel human coronavirus (SARS-CoV). We report herein the method developed to inhibit the main protease of SARS coronavirus.
We used the core structure of a-hydroxy diethyl phosphonate（i）,a-hydroxy amide（ii） and a-keto amide（iii）, respectively, to mimic the tetrahedral transition state of the main protease. Small libraries of protease inhibitors were constructed by using combinatorial chemistry, and some molecules having potent inhibition ability against SARS-CoV 3CLpro were discovered.
More than 20 compounds out of hundreds test samples were shown to have inhibition activities at concentrations <10 uM, and two compounds have inhibition activities at <1 uM. We hope these lead compounds can be developed in future to become therapeutical agents of SARS.
Subjects
蛋白酶
抑制劑
羥基膦酸二乙基酯
酮基醯胺
嚴重急性呼吸道症候群
羥基醯胺
hydroxy diethyl phosphonate
hydroxy amide
Severe Acute Respiratory Syndrome
keto amide
SARS
protease inhibitors
Type
thesis
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