Synthesis and Evaluation of Benzoquinolinone Derivatives as SARS-CoV 3CL Protease Inhibitors
Synthesis and Evaluation of Benzoquinolinone Derivatives as SARS-CoV 3CL Protease Inhibitors
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DOI：
10.5012/bkcs.2010.31.01.087
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发表时间：
2010-01-20
影响因子：
1.7
通讯作者：
Jung, Young-Sik
中科院分区：
文献类型：
--
作者：
Ahn, Tae-Young;Kuo, Chih-Jung;Jung, Young-Sik
为了寻找新的抗SARS冠状病毒药物，我们合成并评价了几种苯并喹啉类化合物作为SARS冠状病毒3C样蛋白酶（3CL-pro）抑制剂。在计算机模拟研究化合物I的两个刚性苯并喹啉酮和N-苯基四唑分别通过氢键和疏水作用与SARS蛋白酶的S1和S2位点结合的基础上，我们设计并合成了两个羟基位点上的烷基化苯并喹啉。我们发现化合物2a对3CLpro的抑制活性比化合物1高5倍。
For the discovery of new antivirals against Severe Acute Respiratory Syndrorne-coronavirus (SARS-CoV), we prepared and evaluated several benzoguinoline compounds as its 3C-like protease (3CL-pro) inhibitors. Based oil the computer modeling Study that each of the two rigid benzoquinolinone and N-phenotetrazole moieties of the compound I is bound to the S I and S2 sites, respectively, of the SARS protease by forming H-bonds and hydrophobic interactions, we designed and synthesized alkylated benzoquinolities at both the sites of the hydroxyl groups. We found that the compound 2a showed five times higher inhibiting activity against the 3CLpro compared to the compound 1.