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Synthesis and PI 3-Kinase Inhibition Activity of Some Novel 2,4,6-Trisubstituted 1,3,5-Triazines

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abstract
A number of new trisubstituted triazine phosphatidylinositol 3-kinase (PI3K) inhibitors were prepared via a three-step procedure utilizing sequential nucleophilic aromatic substitution and cross-coupling reactions. All were screened as PI3K inhibitors relative to the well-characterized PI3K inhibitor, ZSTK474. The most active inhibitors prepared here were 2–4 times more potent than ZSTK474. A leucine linker was attached to the most active inhibitor since it would remain on any peptide-containing prodrug after cleavage by a prostate-specific antigen, and it did not prevent inhibition of protein kinase B (Akt) phosphorylation, and hence, the inhibition of PI3K by the modified inhibitor.
subject
triazine synthesis
PI3K inhibitor
prostate cancer
contributor
Nelson, R. (author)
Schronce, T. (author)
Huang, Y. (author)
Albugami, A. (author)
Kulik, G. (author)
Welker, M. (author)
date
2020-03-09T18:02:47Z (accessioned)
2020-03-09T18:02:47Z (available)
7/4/10 (issued)
identifier
Nelson, R., Schronce, T., Huang, Y., Albugami, A., Kulik, G., & Welker, M. (2018). Synthesis and PI 3-kinase inhibition activity of some novel 2, 4, 6-trisubstituted 1, 3, 5-triazines. Molecules, 23(7), 1628. (citation)
https://doi.org/10.3390/molecules23071628 (doi)
http://hdl.handle.net/10339/96047 (uri)
language
en (iso)
publisher
MDPI
source
Molecules
title
Synthesis and PI 3-Kinase Inhibition Activity of Some Novel 2,4,6-Trisubstituted 1,3,5-Triazines
type
Article

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