Diarylthiophenes as inhibitors of the pore-forming protein perforin

    Thumbnail
    Download
    Citations
    Scopus
    Web of Science
    Altmetric
    11
    10
    Author
    Miller, CK; Huttunen, KM; Denny, WA; Jaiswal, JK; Ciccone, A; Browne, KA; Trapani, JA; Spicer, JA
    Date
    2016-01-15
    Source Title
    Bioorganic and Medicinal Chemistry Letters
    Publisher
    PERGAMON-ELSEVIER SCIENCE LTD
    University of Melbourne Author/s
    Trapani, Joseph
    Affiliation
    Sir Peter MacCallum Department of Oncology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Miller, C. K., Huttunen, K. M., Denny, W. A., Jaiswal, J. K., Ciccone, A., Browne, K. A., Trapani, J. A. & Spicer, J. A. (2016). Diarylthiophenes as inhibitors of the pore-forming protein perforin. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 26 (2), pp.355-360. https://doi.org/10.1016/j.bmcl.2015.12.003.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/258083
    DOI
    10.1016/j.bmcl.2015.12.003
    Abstract
    Evolution from a furan-containing high-throughput screen (HTS) hit (1) resulted in isobenzofuran-1(3H)-one (2) as a potent inhibitor of the function of both isolated perforin protein and perforin delivered in situ by intact KHYG-1 NK cells. In the current study, structure-activity relationship (SAR) development towards a novel series of diarylthiophene analogues has continued through the use of substituted-benzene and -pyridyl moieties as bioisosteres for 2-thioxoimidazolidin-4-one (A) on a thiophene (B) -isobenzofuranone (C) scaffold. The resulting compounds were tested for their ability to inhibit perforin lytic activity in vitro. Carboxamide (23) shows a 4-fold increase over (2) in lytic activity against isolated perforin and provides good rationale for continued development within this class.

    Export Reference in RIS Format     

    Publisher licence
    CC BY
    Collections