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

S Sidique, SA Shiryaev, BI Ratnikov, A Herath…

Index: Sidique, Shyama; Shiryaev, Sergey A.; Ratnikov, Boris I.; Herath, Ananda; Su, Ying; Strongin, Alex Y.; Cosford, Nicholas D.P. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 19 p. 5773 - 5777

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Citation Number: 32

Abstract

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 ...