Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors.
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.
Zhang
Han-Zhong
HZ
Maxim Pharmaceuticals, 6650 Nancy Ridge Drive, San Diego, CA 92121, USA.
Zhang
Hong
H
Kemnitzer
William
W
Tseng
Ben
B
Cinatl
Jindrich
J
Michaelis
Martin
M
Doerr
Hans Wilhelm
HW
Cai
Sui Xiong
SX
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D016923:Cell Death / Q000187:drug effects; D002522:Chlorocebus aethiops; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects*; D014709:Vero Cells; D014779:Virus Replication
D000998:Antiviral Agents; D004151:Dipeptides; C509003:benzyloxycarbonyl-leucyl-N,N-dimethylglutamine fluoromethyl ketone