《The Discovery of 7-Methyl-2-[(7-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino]-9-(tetrahydro-2H-pyran-4-yl)-7,9-dihydro-8H-purin-8-one (AZD7648), a Potent and Selective DNA-Dependent Protein Kinase (DNA-PK) Inhibitor》 was published in Journal of Medicinal Chemistry in 2020. These research results belong to Goldberg, Frederick W.; Finlay, M. Raymond V.; Ting, Attilla K. T.; Beattie, David; Lamont, Gillian M.; Fallan, Charlene; Wrigley, Gail L.; Schimpl, Marianne; Howard, Martin R.; Williamson, Beth; Vazquez-Chantada, Mercedes; Barratt, Derek G.; Davies, Barry R.; Cadogan, Elaine B.; Ramos-Montoya, Antonio; Dean, Emma. Application In Synthesis of trans-4-Aminocyclohexanol The article mentions the following:
DNA-PK is a key component within the DNA damage response, as it is responsible for recognizing and repairing double-strand DNA breaks (DSBs) via non-homologous end joining. Historically it has been challenging to identify inhibitors of the DNA-PK catalytic subunit (DNA-PKcs) with good selectivity vs. the structurally related PI3 (lipid) and PI3K-related protein kinases. We screened our corporate collection for DNA-PKcs inhibitors with good PI3 kinase selectivity, identifying compound 1. Optimization focused on further improving selectivity while improving phys. and pharmacokinetic properties, notably co-optimization of permeability and metabolic stability, to identify compound 16 (AZD7648). Compound 16 had no significant off-target activity in the protein kinome and only weak activity vs. PI3Kα/γ lipid kinases. Monotherapy activity in murine xenograft models was observed, and regressions were observed when combined with inducers of DSBs (doxorubicin or irradiation) or PARP inhibition (olaparib). These data support progression into clin. studies (NCT03907969). In addition to this study using trans-4-Aminocyclohexanol, there are many other studies that have used trans-4-Aminocyclohexanol(cas: 27489-62-9Application In Synthesis of trans-4-Aminocyclohexanol) was used in this study.
trans-4-Aminocyclohexanol(cas: 27489-62-9) belongs to anime. Hydrogen peroxide (H2O2) and peroxy acids generally add an oxygen atom to the nitrogen of amines. With primary amines, this step is normally followed by further oxidation, leading to nitroso compounds, RNO, or nitro compounds, RNO2. Secondary amines are converted to hydroxylamines, R2NOH, and tertiary amines to amine oxides, R3NO.Application In Synthesis of trans-4-Aminocyclohexanol
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