Design and synthesis of cinanserin analogs as severe acute respiratory syndrome coronavirus 3CL protease inhibitors

Qingang Yang; Lili Chen; Xuchang He; Zhenting Gao; Xu Shen; Donglu Bai

doi:10.1248/cpb.56.1400

Design and synthesis of cinanserin analogs as severe acute respiratory syndrome coronavirus 3CL protease inhibitors

Chem Pharm Bull (Tokyo). 2008 Oct;56(10):1400-5. doi: 10.1248/cpb.56.1400.

Authors

Qingang Yang¹, Lili Chen, Xuchang He, Zhenting Gao, Xu Shen, Donglu Bai

Affiliation

¹ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

PMID: 18827378
DOI: 10.1248/cpb.56.1400

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.

MeSH terms

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

Substances

Antiviral Agents
Indicators and Reagents
Protease Inhibitors
Serotonin Antagonists
Viral Proteins
Cysteine Endopeptidases
Coronavirus 3C Proteases
Cinanserin