Synthesis and evaluation of pyrazolone compounds as SARS-coronavirus 3C-like protease inhibitors

R Ramajayam; Kian-Pin Tan; Hun-Ge Liu; Po-Huang Liang

doi:10.1016/j.bmc.2010.09.050

Synthesis and evaluation of pyrazolone compounds as SARS-coronavirus 3C-like protease inhibitors

Bioorg Med Chem. 2010 Nov 15;18(22):7849-54. doi: 10.1016/j.bmc.2010.09.050. Epub 2010 Sep 25.

Authors

R Ramajayam¹, Kian-Pin Tan, Hun-Ge Liu, Po-Huang Liang

Affiliation

¹ Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Taipei 11529, Taiwan.

Abstract

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.

MeSH terms

3C Viral Proteases
Antiviral Agents / chemical synthesis*
Antiviral Agents / chemistry
Antiviral Agents / pharmacology
Binding Sites
Catalytic Domain
Computer Simulation
Coronavirus 3C Proteases
Cysteine Endopeptidases / metabolism
Enterovirus B, Human / enzymology
Humans
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology
Pyrazolones / chemical synthesis
Pyrazolones / chemistry*
Pyrazolones / pharmacology
Structure-Activity Relationship
Viral Proteins / antagonists & inhibitors*
Viral Proteins / metabolism

Substances

Antiviral Agents
Protease Inhibitors
Pyrazolones
Viral Proteins
Cysteine Endopeptidases
3C Viral Proteases
Coronavirus 3C Proteases