Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors was written by Xiao, Yufang;Huck, Bayard R.;Lan, Ruoxi;DeSelm, Lizbeth;Chen, Xiaoling;Qiu, Hui;Neagu, Constantin;Johnson, Theresa;Mochalkin, Igor;Gardberg, Anna;Jiang, Xuliang;Tian, Hui;Dutt, Vikram;Santos, Dusica;Head, Jared;Jackson, Jennifer;Syed, Sakeena;Lin, Jing;Wilker, Erik;Ma, Jianguo;Clark, Anderson;Machl, Andreas;Bankston, Donald;Jones, Christopher C. V.;Goutopoulos, Andreas;Sherer, Brian. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2021.Safety of 4-Amino-6-chloropyrimidine-5-carbonitrile This article mentions the following:
Activation of the PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block neg. impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 6-[4-(2-Amino-1-phenyl-ethyl)-piperazin-1-yl]-5-(4-fluoro-phenyl)-pyrimidin-4-ylamine, which showed a single-digit nanomolar and a micromolar potencies in p70S6K and Akt enzymic assays. SAR optimization improved Akt enzymic and p70S6K cellular potencies, reduced hERG liability, and ultimately discovered the promising candidate 4-Amino-6-{4-[1-(2-azetidin-1-yl-ethyl)-4-(4-fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidin-1-yl}pyrimidine-5-carboxylic acid amide, which exhibited with a single digit nanomolar value in both p70S6K and Akt biochem. assays, and hERG activities (IC50 = 17.4 μM). This agent demonstrated dose-dependent efficacy in inhibiting mice breast cancer tumor growth and covered more than 90% pS6 inhibition up to 24 h at a dose of 200 mg/kg po. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Safety of 4-Amino-6-chloropyrimidine-5-carbonitrile).
4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) belongs to nitriles. Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities, often in the 30s. Nitrile groups in organic compounds can undergo a variety of reactions depending on the reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion.Safety of 4-Amino-6-chloropyrimidine-5-carbonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts