Design, synthesis, and evaluation of trifluoromethyl ketones as inhibitors of SARS-CoV 3CL protease

被引：71

作者：

Shao, Yi-Ming ^{[1
,2
,3
]}

Yang, Wen-Bin ^{[1
]}

Kuo, Tun-Hsun ^{[2
]}

Tsai, Keng-Chang ^{[1
]}

Lin, Chun-Hung ^{[1
,2
,3
]}

Yang, An-Suei ^{[1
]}

Liang, Po-Huang ^{[1
,2
,3
]}

Wong, Chi-Huey ^{[1
,2
,3
,4
]}

机构：

[1] Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan

[2] Acad Sinica, Inst Biol Chem, Taipei 11529, Taiwan

[3] Natl Taiwan Univ, Inst Biochem Sci, Taipei 10617, Taiwan

[4] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 08期

关键词：

SARS; protease inhibitor; trifluoromethyl ketone; time-dependent inhibition;

D O I：

10.1016/j.bmc.2008.02.040

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of trifluoromethyl ketones as SARS-CoV 3CL protease inhibitors was developed. The inhibitors were synthesized in four steps from commercially available compounds. Three different amino acids were explored in the P1-position and in the P2-P4 positions varying amino acids and long alkyl chain were incorporated. All inhibitors were evaluated in an in vitro assay using purified enzyme and fluorogenic substrate peptide. One of the inhibitors showed a time-dependent inhibition, with a K-i value of 0.3 mu M after 4 h incubation. (c) 2008 Published by Elsevier Ltd.

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收藏

页码：4652 / 4660

页数：9

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