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ID: ALA1151924

Journal: Bioorg Med Chem Lett

Title: Characterization of lassa virus cell entry inhibitors: determination of the active enantiomer by asymmetric synthesis.

Authors: Whitby LR, Lee AM, Kunz S, Oldstone MB, Boger DL.

Abstract: The comparative characterization of a series of 4-acyl-1,6-dialkylpiperazin-2-ones as potent cell entry inhibitors of the hemorrhagic fever arenavirus Lassa (LASV) is disclosed. The resolution and examination of the individual enantiomers of the prototypical LASV cell entry inhibitor 3 (16G8) is reported and the more potent (-)-enantiomer was found to be 15-fold more active than the corresponding (+)-enantiomer. The absolute configuration of (-)-3 was established by asymmetric synthesis of the active inhibitor (-)-(S)-3 (lassamycin-1). A limited deletion scan of lassamycin-1 defined key structural features required of the prototypical inhibitors.

CiteXplore: 19428249

DOI: 10.1016/j.bmcl.2009.04.098