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Design and synthesis of cinanserin analogs as severe acute respiratory syndrome coronavirus 3CL protease inhibitors.
Yang, Qingang; Chen, Lili; He, Xuchang; Gao, Zhenting; Shen, Xu; Bai, Donglu.
Chem Pharm Bull (Tokyo) ; 56(10): 1400-5, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18827378

ABSTRACT

The severe acute respiratory syndrome (SARS) coronavirus 3CL protease is an attractive target for the development of anti-SARS drugs. In this paper, cinanserin (1) analogs were synthesized and tested for the inhibitory activities against SARS-coronavirus (CoV) 3CL protease by fluorescence resonance energy transfer (FRET) assay. Four analogs show significant activities, especially compound 26 with an IC(50) of 1.06 microM.


Subject(s)
Antiviral Agents/pharmacology , Cinanserin/analogs & derivatives , Cinanserin/pharmacology , Protease Inhibitors/pharmacology , Serotonin Antagonists/pharmacology , Severe acute respiratory syndrome-related coronavirus/enzymology , Viral Proteins/antagonists & inhibitors , Antiviral Agents/chemical synthesis , Cinanserin/chemical synthesis , Coronavirus 3C Proteases , Cysteine Endopeptidases , Drug Design , Fluorescence Resonance Energy Transfer , Indicators and Reagents , Magnetic Resonance Spectroscopy , Models, Molecular , Protease Inhibitors/chemical synthesis , Serotonin Antagonists/chemical synthesis , Spectrophotometry, Infrared , Structure-Activity Relationship
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