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.

Synthesis of Luminescent Fused Imidazole Bicyclic Acetic Esters by a Multicomponent Palladium Iodide‐Catalyzed Oxidative Alkoxycarbonylation Approach

“…Substrates 1 a – b , 1 g , 1 l and 1 i were prepared according a known procedure starting from corresponding 2‐aminopyridine [6a] . Substrate 1 k was prepared according a known procedure starting from 2,4,6‐trichloropyrimidine [13] . Substrate 1 c – f , 1 h and 1 j were prepared as described below.…”