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Molecules 2018, 23(7), 1675;

Synthesis and PI3 Kinase Inhibition Activity of Some Novel Trisubstituted Morpholinopyrimidines

Department of Chemistry, Wake Forest University, P.O. Box 7486, Winston-Salem, NC 27109, USA
Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA
Life Sciences Program, College of Science, Alfaisal University, Riyadh 11533, Saudi Arabia
Authors to whom correspondence should be addressed.
Received: 28 June 2018 / Revised: 5 July 2018 / Accepted: 7 July 2018 / Published: 10 July 2018
(This article belongs to the Section Medicinal Chemistry)
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A number of new substituted morpholinopyrimidines were prepared utilizing sequential nucleophilic aromatic substitution and cross-coupling reactions. One of the disubstituted pyrimidines was converted into two trisubstituted compounds which were screened as PI3K inhibitors relative to the well-characterized PI3K inhibitor ZSTK474, and were found to be 1.5–3-times more potent. A leucine linker was attached to the most active inhibitor since it would remain on any peptide-containing prodrug after cleavage by prostate-specific antigen, and it did not prevent inhibition of AKT phosphorylation and hence the inhibition of PI3K by the modified inhibitor. View Full-Text
Keywords: triazine synthesis; PI3K inhibitor; prostate cancer triazine synthesis; PI3K inhibitor; prostate cancer

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Wright, E.W.; Nelson, R.A., Jr.; Karpova, Y.; Kulik, G.; Welker, M.E. Synthesis and PI3 Kinase Inhibition Activity of Some Novel Trisubstituted Morpholinopyrimidines. Molecules 2018, 23, 1675.

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