Synthesis and biological evaluation of 4-morpholino-2-phenylquinazolines and related derivatives as novel PI3 kinase p110α inhibitors

A series of 4-morpholino-2-phenylquinazolines and related derivatives were prepared and evaluated as inhibitors of PI3 kinase p110α. In this series, the thieno[3,2-d]pyrimidine derivative 15e showed the strongest inhibitory activity against p110α, with an IC50 value of 2.0 nM, and inhibited proliferation of A375 melanoma cells with an IC50 value of 0.58 μM. Moreover, 15e was found to be selective for p110α over other PI3K isoforms and protein kinases, making it the first example of a selective PI3K p110α inhibitor.

The thieno[3,2-d]pyrimidine derivative 15e is a potent and selective p110α inhibitor.Figure optionsDownload as PowerPoint slide