Exploiting the Biginelli reaction: nitrogen-rich pyrimidine-based tercyclic alpha-helix mimetics
- Author(s)
- Lim, Z; Duggan, PJ; Wan, SS; Lessene, G; Meyer, AG; Tuck, KL;
- Details
- Publication Year 2016,Volume 72,Issue #9,Page 1151-1160
- Journal Title
- Tetrahedron
- Publication Type
- Journal Article
- Abstract
- Several rationally designed pyrimidine-based scaffolds intended to mimic the spatial projection of the i, i+3, and i+7 residues of an alpha-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 alpha-helix mimetics. A pyrimidine-based scaffold designed to mimic the alpha-helical BH3 domain of the pro-apoptotic Bak protein was also prepared as a putative inhibitor of the BcI-x(L)/Bak protein-protein interaction. The pyrimidine-based tercyclic alpha-helix mimetics, and the putative Bcl-x(L) inhibitor, were assessed using a luminescence competition assay, however, none displayed inhibitory activity against Bel-x(L) or Mcl-1. (C) 2016 Elsevier Ltd. All rights reserved.
- Publisher
- Elsevier
- Research Division(s)
- Chemical Biology
- Publisher's Version
- https://doi.org/10.1016/j.tet.2015.12.044
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-06-15 08:51:08
Last Modified: 2016-06-15 09:11:03