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Synthesis and PI3 Kinase Inhibition Activity of Some Novel Trisubstituted Morpholinopyrimidines.

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.

SUBMITTER: Wright EW

PROVIDER: S-EPMC6100461 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Synthesis and PI3 Kinase Inhibition Activity of Some Novel Trisubstituted Morpholinopyrimidines.

Wright Emily W EW Nelson Ronald A RA Karpova Yelena Y Kulik George G Welker Mark E ME

Molecules (Basel, Switzerland) 20180710 7

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 ...[more]

PMID: 29996482

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