Next Article in Journal
The Current Status of Heterogeneous Palladium Catalysed Heck and Suzuki Cross-Coupling Reactions
Previous Article in Journal
Efficacy of Prosopilosidine from Prosopis glandulosa var. glandulosa against Cryptococcus neoformans Infection in a Murine Model
Article Menu

Export Article

Open AccessArticle
Molecules 2018, 23(7), 1675; https://doi.org/10.3390/molecules23071675

Synthesis and PI3 Kinase Inhibition Activity of Some Novel Trisubstituted Morpholinopyrimidines

1
Department of Chemistry, Wake Forest University, P.O. Box 7486, Winston-Salem, NC 27109, USA
2
Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA
3
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)
View Full-Text   |   Download PDF [1468 KB, uploaded 10 July 2018]   |  

Abstract

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
Figures

Graphical abstract

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).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top