title: Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors.
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.
authors.affiliation: Maxim Pharmaceuticals, 6650 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Han-Zhong
authors.initials: HZ
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: William
authors.initials: W
authors.lastname: Kemnitzer
authors.forename: Ben
authors.initials: B
authors.lastname: Tseng
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.forename: Hans Wilhelm
authors.initials: HW
authors.lastname: Doerr
authors.forename: Sui Xiong
authors.initials: SX
authors.lastname: Cai
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D004151:Dipeptides; C509003:benzyloxycarbonyl-leucyl-N,N-dimethylglutamine fluoromethyl ketone