benzoic-acid-[5-amino-1-(4-methoxyphenyl)sulfonyl-3-pyrazolyl]-ester and West-Nile-Fever

West Nile Virus (WNV) is a potentially deadly mosquito-borne flavivirus which has spread rapidly throughout the world. Currently there is no effective vaccine against flaviviral infections. We previously reported the identification of pyrazole ester derivatives as allosteric inhibitors of WNV NS2B-NS3 proteinase. These compounds degrade rapidly in pH 8 buffer with a half life of 1-2h. We now report the design, synthesis and in vitro evaluation of pyrazole derivatives that are inhibitors of WNV NS2B-NS3 proteinase with greatly improved stability in the assay medium.

Topics: Allosteric Regulation; Antiviral Agents; Drug Design; Half-Life; Hydrogen-Ion Concentration; Hydrolysis; Pyrazoles; RNA Helicases; Serine Endopeptidases; Serine Proteinase Inhibitors; Structure-Activity Relationship; Viral Nonstructural Proteins; West Nile Fever; West Nile virus