Reference of 35857-89-7, Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Article, and a compound is mentioned, 35857-89-7, 6-Chloropyridazine-3-carbonitrile, introducing its new discovery.
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 muM), 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 muM) 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 muM. This study identified these structural classes as novel DNA-PK inhibitors and delineated initial structure-activity relationships against DNA-PK.
Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law.Reference of 35857-89-7. In my other articles, you can also check out more blogs about 35857-89-7
Reference：
Pyridazine – Wikipedia,
Pyridazine | C4H4N929 – PubChem