168425-64-7

Usage

Uses

Compound 401 is a selective inhibitor of DNA-PK and FRAP.

Biological Activity

Reversible and selective inhibitor of DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR) (IC 50 values are 0.28 and 5.3 μ M respectively). Displays little affinity for other commonly studied kinases including PI 3-K, ATM and ATR (IC 50 values are all > 100 μ M). Induces apoptosis in vitro .

InChI:InChI=1/C16H15N3O2/c20-15-11-14(18-7-9-21-10-8-18)17-16-13-4-2-1-3-12(13)5-6-19(15)16/h1-6,11H,7-10H2

Upstream product

• 110-91-8 morpholine 
• 100441-19-8 ethyl 2-(isoquinolin-1-yl)-5-oxo-2,5-dihydroisoxazole-4-carboxylate 
• 37714-64-0 3-(4-Morpholinyl)-3-oxopropansaeure-ethylester 
• 23212-58-0 pyrimido[2,1-a]isoquinoline-2,4-dione 
• 1532-84-9 isoquinolin-1-ylamine 
• 670-80-4 4-cyclohexen-1-ylmorpholine 
• 42398-55-0 2-chloro-4H-pyrimido<2,1-a>isoquinolin-4-one 

Relevant academic research and scientific papers

1,2-Fused pyrimidines VII. 3-(dialkylamino)-1H-pyrimido[1,2-a]quinolin-1-ones and 2-(dialkylamino)-4H-pyrimido[2,1-a]isoquinolin-4-ones as antiplatelet compounds

A number of 3-(dialkylamino)-1H-pyrimido[1,2-a]quinolin-1-ones 3 and 2-(dialkylamino)-4H-pyrimido[2,1-a]isoquinolin-4-ones 4 were prepared by treating the corresponding chloro derivatives with an excess of dialkylamines. The highest in vitro antiplatelet

Selective benzopyranone and pyrimido[2,1-α]isoquinolin-4-one inhibitors of DNA-dependent protein kinase: Synthesis, structure-activity studies, and radiosensitization of a human tumor cell line in vitro

A diverse range of chromen-2-one, chromen-4-one and pyrimidoisoquinolin-4- one derivatives was synthesized and evaluated for inhibitory activity against the DNA repair enzyme DNA-dependent protein kinase (DNA-PK), with a view to elucidating structure-activity relationships for potency and kinase selectivity. DNA-PK inhibitory activity varied widely over the series of compounds evaluated (IC50 values ranged from 0.19 to >10 μM), with excellent activity being observed for the 7,8-benzochromen-4-one and pyrimido[2,1-a] isoquinolin-4-one templates. By contrast, inhibitors based on the benzochromen-2-one (coumarin) or 2-aryl-7,8-benzochromen-4-one (flavone) scaffolds were less potent. Crucially, these studies revealed a very constrained structure-activity relationship at the 2-position of the benzopyranone and pyrimido[2,1-a]-isoquinolin-4-one pharmacophore, with only a 2-morpholino or 2-(2′-methylmorpholino) group being tolerated at this position. More detailed biological studies conducted with the most potent inhibitor NU7163 (48; IC50 = 0.19 μM) demonstrated ATP-competitive DNA-PK inhibition, with a Ki value of 24 nM, and 48 exhibited selectivity for DNA-PK compared with the related enzymes ATM, ATR, mTOR, and PI 3-K (p110alpha). Compound 48 sensitized the HeLa human tumor cell line to the cytotoxic effects of ionizing radiation in vitro, a dose modification factor of 2.3 at 10% survival being observed with an inhibitor concentration of 5 μM. This study identified these structural classes as novel DNA-PK inhibitors and delineated initial structure-activity relationships against DNA-PK.

The chemistry of 5-oxodihydroisoxazoles. XXI: Amidines and pyrimidin-4-ones from the reaction of isoxazol-5(2H)-ones with amines

While isoxazol-5(2H)-ones substituted with heterocycles at C2 but unsubstituted at C3 react with amines to give either amidines or malonamides, their reaction at low temperatures with lithium dialkylamides is a preparatively useful procedure for obtaining the amidines in most cases. Longer reaction, times may lead to formation of pyrimidin-4-ones when ester groups are present at C 4 of the isoxazolone.

The chemistry of 5-oxodihydroisoxazoles. XV reaction of derived ketenimines with enamines and enolates

Reaction of 2-heterocyclisoxazol-5(2H)-ones with bases leads to the formation of ketenimines, which react with nucleophiles in competition with intramolecular reactions. Such reactions in the presence of enamines, enamine anions or enolates are reported.