Exploiting the Biginelli reaction: Nitrogen-rich pyrimidine-based tercyclic α-helix mimetics

Zelong Lim, Peter Duggan, Soo Wan, Guillaume Lessene, Adam Meyer, Kellie Tuck

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    Several rationally designed pyrimidine-based scaffolds intended to mimic the spatial projection of the i, i+3, and i+7 residues of an α-helix and also possess improved aqueous solubility were prepared. A Biginelli-oxidation process was used to form the central pyrimidine ring of these scaffolds, which was subsequently manipulated to form pyrimidine-based tercyclic α-helix mimetics. A pyrimidine-based scaffold designed to mimic the α-helical BH3 domain of the pro-apoptotic Bak protein was also prepared as a putative inhibitor of the Bcl-xL/Bak protein-protein interaction. The pyrimidine-based tercyclic α-helix mimetics, and the putative Bcl-xL inhibitor, were assessed using a luminescence competition assay, however, none displayed inhibitory activity against Bcl-xL or Mcl-1.

    Original languageEnglish
    Pages (from-to)1151-1160
    Number of pages10
    JournalTetrahedron
    Volume72
    Issue number9
    DOIs
    Publication statusPublished - 3 Mar 2016

    Keywords

    • Alpha-helix mimetics
    • Bcl-x inhibitor
    • Biginelli reaction
    • Pyrimidine

    Fingerprint Dive into the research topics of 'Exploiting the Biginelli reaction: Nitrogen-rich pyrimidine-based tercyclic α-helix mimetics'. Together they form a unique fingerprint.

  • Cite this