Discovery of a series of 8-(2,3-dihydro-1,4-benzoxazin-4-ylmethyl)-2-morpholino-4-oxo-chromene-6-carboxamides as PI3Kβ/δ inhibitors for the treatment of PTEN-deficient tumours

[Display omitted] We report the discovery and optimisation of a series of 8-(2,3-dihydro-1,4-benzoxazin-4-ylmethyl)-2-morpholino-4-oxo-chromene-6-carboxamides, leading to compound 16 as a potent and selective PI3Kβ/δ inhibitor: PI3Kβ cell IC50 0.012μM (in PTEN null MDA-MB-468 cell) and PI3Kδ cell IC...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2016-05, Vol.26 (9), p.2318-2323
Hauptverfasser:	Barlaam, Bernard, Cosulich, Sabina, Degorce, Sébastien, Fitzek, Martina, Green, Stephen, Hancox, Urs, Lambert-van der Brempt, Christine, Lohmann, Jean-Jacques, Maudet, Mickaël, Morgentin, Rémy, Péru, Aurélien, Plé, Patrick, Saleh, Twana, Ward, Lara, Warin, Nicolas
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Cell Line, Tumor Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Humans Isoenzymes - antagonists & inhibitors Mice Morpholinos - chemistry Morpholinos - pharmacology Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphorylation PI3Kβ/δ inhibitor PTEN Phosphohydrolase - genetics PTEN-deficient tumours Rational design
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