Design and synthesis of cinanserin analogs as severe acute respiratory syndrome coronavirus 3CL protease inhibitors.
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.
Yang
Qingang
Q
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Chen
Lili
L
He
Xuchang
X
Gao
Zhenting
Z
Shen
Xu
X
Bai
Donglu
D
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002928:Cinanserin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases; D015195:Drug Design; D031541:Fluorescence Resonance Energy Transfer; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000201:enzymology*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
D000998:Antiviral Agents; D007202:Indicators and Reagents; D011480:Protease Inhibitors; D012702:Serotonin Antagonists; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases; D002928:Cinanserin