Rick Morrison, J. Al-Rawi
Jun 2, 2016
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Influential Citations
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Journal
Journal of Enzyme Inhibition and Medicinal Chemistry
Abstract
Abstract Coumarin, a naturally occurring or synthesised phytochemical, displays a wide range of biological activities. However, chromen-2-ones fused with 1,3-benzoxazine rings is not well documented and there is a gap in the literature which required engaging. The substituted-2-thioxo-chromen-oxazine linear compounds 14a–i and angular compounds 16a–e were synthesised from the reaction of hydroxy-substituted-chromene-carboxylic 10–13 with freshly prepared Ph3P(SCN)2. 2-Morpholino-substituted-chromen-oxazine-4,8-dione and 8-morpholino-substituted-chromen-oxazine-2,10-dione 15a–f and 17 were synthesised from the reaction of the corresponding oxazines 14 and 16 with morpholine. PI3K activity was observed for the hydroxy-substituted-chromene-carboxylic acid of which compound 13b showed moderate PI3Kγ (IC50 = 5.56 μM) and PI3Kα (IC50 = 14.7 μM) activity. Additionally, 8-morpholino-chromen-oxazine-2,10-dione 17a showed isoform selective PI3Kδ activity with IC50 = 5.08 μM with non-DNA-PK ≥ 100 μM. Consequently compound 17a can be considered as a selective PI3Kδ inhibitor with non-DNA-PK at compound concentrations ≥100 μM.