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http://dx.doi.org/10.5012/bkcs.2010.31.01.087

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

Ahn, Tae-Young (Bio-organic Science Division, Korea Research Institute of Chemical Technology)
Kuo, Chih-Jung (Institute of Biological Chemistry)
Liu, Hun-Ge (Institute of Biological Chemistry)
Ha, Deok-Chan (Department of Chemistry, Korea University)
Liang, Po-Huang (Institute of Biological Chemistry)
Jung, Young-Sik (Bio-organic Science Division, Korea Research Institute of Chemical Technology)
Publication Information
Bulletin of the Korean Chemical Society / v.31, no.1, 2010 , pp. 87-91 More about this Journal
Abstract
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.
Keywords
Benzoquinoline; Coronavirus; Picornavirus; 3C protease; Computer modeling;
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