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

Zelong Lim, Peter J. Duggan, Soo San Wan, Guillaume Lessene, Adam G. Meyer, Kellie L. Tuck

Research output: Contribution to journalArticleResearchpeer-review

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

Cite this