Structure-activity relationship and improved hydrolytic stability of pyrazole derivatives that are allosteric inhibitors of West Nile Virus NS2B-NS3 proteinase

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Sidique, Shyama^1,2  Shiryaev, Sergey A.²  Ratnikov, Boris I.²  Herath, Ananda^1,2  Su, Ying^1,2  Strongin, Alex Y.²  Cosford, Nicholas D. P.^1,2 

[1] Conrad Prebys Ctr Chem Genom, La Jolla, CA 92037 USA

[2] Burnham Inst Med Res, La Jolla, CA 92037 USA

关键词: West Nile virus;    Flavivirus;    Proteinase inhibitors;    NS2B-NS3 proteinase;    Antiviral;   

DOI  :  10.1016/j.bmcl.2009.07.150

来源: Elsevier

【 摘 要 】

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 1-2 h. 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. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

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