59197-90-9Relevant articles and documents
Heteroaromatic ester inhibitors of hepatitis A virus 3C proteinase: Evaluation of mode of action
Huitema, Carly,Zhang, Jianmin,Yin, Jiang,James, Michael N.G.,Vederas, John C.,Eltis, Lindsay D.
, p. 5761 - 5777 (2008/12/21)
The related 3C and 3C-like proteinase (3Cpro and 3CLpro) of picornaviruses and coronaviruses, respectively, are good drug targets. As part of an effort to generate broad-spectrum inhibitors of these enzymes, we screened a library of inhibitors based on a halopyridinyl ester from a previous study of the severe acute respiratory syndrome (SARS) 3CL proteinase against Hepatitis A virus (HAV) 3Cpro. Three of the compounds, which also had furan rings, inhibited the cleavage activity of HAV 3Cpro with Kics of 120-240 nM. HPLC-based assays revealed that the inhibitors were slowly hydrolyzed by both HAV 3Cpro and SARS 3CLpro, confirming the identity of the expected products. Mass spectrometric analyses indicated that this hydrolysis proceeded via an acyl-enzyme intermediate. Modeling studies indicated that the halopyridinyl moiety of the inhibitor fits tightly into the S1-binding pocket, consistent with the lack of tolerance of the inhibitors to modification in this portion of the molecule. These compounds are among the most potent non-peptidic inhibitors reported to date against a 3Cpro.
3-Quinoline-substituted 4-oxy-carboxamides
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, (2008/06/13)
Novel 3-quinoline-carboxamides of the formula SPC1 Wherein R is selected from the group consisting of halogen, --CF3, --OCF3 and --SCF3 in the 7- or 8-position, R1 is selected from the group consisting of hydrogen and acyl of an aliphatic carboxylic acid of 2 to 4 carbon atoms, R3 is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms and R2 is selected from the group consisting of thiazloyl, pyridinyl and oxazolyl and their non-toxic, pharmaceutically acceptable acid addition salts having analgesic activity and their preparation and novel intermediates.
