SARS冠狀病毒蛋白?抑制劑之開發與合成

Synthesis of SARS Coronavirus Main Protease Inhibitors as anti-SARS Therapeutic Agents

陳吉峰(GeeFong Chen)

指導教授 ： 陳家俊

國立臺灣師範大學/理學院/化學系/碩士(2003年)

摘要

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關鍵字

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並列摘要

SARS (Severe Acute Respiratory Syndrome) is an infectious disease caused by a novel human coronavirus. SARS-CoV Mpro is a crucial protease in the virus’s replication cycle. By a understanding of SARS-CoV Mpro catalysis and a full substrate specificity spectrum for SARS-CoV Mpro, we hope to design and synthesize inhibitors against SARS. We applied the Passerini reaction to form five α-hydroxyl amide core structures and followed by formation of another amide bond to generate five α-hydroxyl amide libraries. Eight hundred compounds were synthesized and their activities against SARS-CoV Mpro were screened. Few compounds of the library members show their IC50 less than 10 μΜ. In the fourth series, we’ve found that compounds 35-B8 and 35-B5 showed strong inhibition (IC50 = 0.9、1.4μΜ) for SARS main protease. Then use compounds 35-B8 and 35-B5 as cores, its C-terminal can be further modified by amide or ester bond formation to yield new libraries. By means of this approach, the best SARS-CoV Mpro inhibitors were screened and obtained.

並列關鍵字

Severe Acute Respiratory Syndrome

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