Synthesis and Evaluation of Benzoquinolinone Derivatives as SARS-CoV 3CL Protease Inhibitors

Bulletin of the Korean chemical society

Young Sik Jung¹  Deok Chan Ha¹  Chih Jung Kuo¹  Hun Ge Liu¹  Po Huang Liang¹  Tae Young Ahn¹ 

关键词: Benzoquinoline;    Coronavirus;    Picornavirus;    3C protease;    Computer modeling;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

For the discovery of new antivirals against Severe Acute Respiratory Syndrome-coronavirus (SARS-CoV), we prepared and evaluated several benzoquinoline compounds as its 3C-like protease (3CLpro) inhibitors. Based on the computer modeling study that each of the two rigid benzoquinolinone and N-phenoltetrazole moieties of the compound 1 is bound to the S1 and S2 sites, respectively, of the SARS protease by forming H-bonds and hydrophobic interactions, we designed and synthesized alkylated benzoquinolines 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.

【 授权许可】

Unknown