Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors.
Identifieur interne : 002358 ( PubMed/Corpus ); précédent : 002357; suivant : 002359Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors.
Auteurs : Han-Zhong Zhang ; Hong Zhang ; William Kemnitzer ; Ben Tseng ; Jindrich Cinatl ; Martin Michaelis ; Hans Wilhelm Doerr ; Sui Xiong CaiSource :
- Journal of medicinal chemistry [ 0022-2623 ] ; 2006.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (chemical synthesis), Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Caco-2 Cells, Cell Death (drug effects), Chlorocebus aethiops, Dipeptides (chemical synthesis), Dipeptides (chemistry), Dipeptides (pharmacology), Drug Design, Humans, SARS Virus (drug effects), Vero Cells, Virus Replication.
- MESH :
- chemical , chemical synthesis : Antiviral Agents, Dipeptides.
- chemical , chemistry : Antiviral Agents, Dipeptides.
- chemical , pharmacology : Antiviral Agents, Dipeptides.
- drug effects : Cell Death, SARS Virus.
- Animals, Caco-2 Cells, Chlorocebus aethiops, Drug Design, Humans, Vero Cells, Virus Replication.
Abstract
This paper describes the design and synthesis of dipeptidyl N,N-dimethyl glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV-induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk (6a) was found to be a potent inhibitor with low toxicity in cells, protecting cells with an EC(50) value of 2.5 microM and exhibiting a selectivity index of >40.
DOI: 10.1021/jm0507678
PubMed: 16451084
Links to Exploration step
pubmed:16451084Le document en format XML
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<author><name sortKey="Zhang, Han Zhong" sort="Zhang, Han Zhong" uniqKey="Zhang H" first="Han-Zhong" last="Zhang">Han-Zhong Zhang</name>
<affiliation><nlm:affiliation>Maxim Pharmaceuticals, 6650 Nancy Ridge Drive, San Diego, CA 92121, USA.</nlm:affiliation>
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<author><name sortKey="Zhang, Hong" sort="Zhang, Hong" uniqKey="Zhang H" first="Hong" last="Zhang">Hong Zhang</name>
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<author><name sortKey="Kemnitzer, William" sort="Kemnitzer, William" uniqKey="Kemnitzer W" first="William" last="Kemnitzer">William Kemnitzer</name>
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<author><name sortKey="Tseng, Ben" sort="Tseng, Ben" uniqKey="Tseng B" first="Ben" last="Tseng">Ben Tseng</name>
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<author><name sortKey="Cinatl, Jindrich" sort="Cinatl, Jindrich" uniqKey="Cinatl J" first="Jindrich" last="Cinatl">Jindrich Cinatl</name>
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<author><name sortKey="Michaelis, Martin" sort="Michaelis, Martin" uniqKey="Michaelis M" first="Martin" last="Michaelis">Martin Michaelis</name>
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<author><name sortKey="Doerr, Hans Wilhelm" sort="Doerr, Hans Wilhelm" uniqKey="Doerr H" first="Hans Wilhelm" last="Doerr">Hans Wilhelm Doerr</name>
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<term>Cell Death (drug effects)</term>
<term>Chlorocebus aethiops</term>
<term>Dipeptides (chemical synthesis)</term>
<term>Dipeptides (chemistry)</term>
<term>Dipeptides (pharmacology)</term>
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<term>Humans</term>
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<front><div type="abstract" xml:lang="en">This paper describes the design and synthesis of dipeptidyl N,N-dimethyl glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV-induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk (6a) was found to be a potent inhibitor with low toxicity in cells, protecting cells with an EC(50) value of 2.5 microM and exhibiting a selectivity index of >40.</div>
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<Abstract><AbstractText>This paper describes the design and synthesis of dipeptidyl N,N-dimethyl glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV-induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk (6a) was found to be a potent inhibitor with low toxicity in cells, protecting cells with an EC(50) value of 2.5 microM and exhibiting a selectivity index of >40.</AbstractText>
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