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.
journal_name
J Enzyme Inhib Med Chemjournal_title
Journal of enzyme inhibition and medicinal chemistryauthors
Morrison R,Al-Rawi JMdoi
10.1080/14756366.2016.1190710subject
Has Abstractpub_date
2016-01-01 00:00:00pages
86-95issue
sup2eissn
1475-6366issn
1475-6374journal_volume
31pub_type
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