Synthesis and evaluation of pyrazolone compounds as SARS-coronavirus 3C-like protease inhibitors.
A series of pyrazolone compounds as possible SARS-CoV 3CL protease inhibitors were designed, synthesized, and evaluated by in vitro protease assay using fluorogenic substrate peptide in which several showed potent inhibition against the 3CL protease. Interestingly, one of the inhibitors was also active against 3C protease from coxsackievirus B3. These inhibitors could be potentially developed into anti-coronaviral and anti-picornaviral agents.
Ramajayam
R
R
Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Taipei 11529, Taiwan.
Tan
Kian-Pin
KP
Liu
Hun-Ge
HG
Liang
Po-Huang
PH
D000086042:3C Viral Proteases; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000378:metabolism; D029822:Enterovirus B, Human / Q000201:enzymology; D006801:Humans; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047069:Pyrazolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000998:Antiviral Agents; D011480:Protease Inhibitors; D047069:Pyrazolones; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; D000086782:Coronavirus 3C Proteases