Development of novel urea-based ATM kinase inhibitors with subnanomolar cellular potency and high kinome selectivity was written by Dimitrov, Teodor;Anli, Cetin;Moschopoulou, Athina Anastasia;Kronenberger, Thales;Kudolo, Mark;Geibel, Christian;Schwalm, Martin Peter;Knapp, Stefan;Zender, Lars;Forster, Michael;Laufer, Stefan. And the article was included in European Journal of Medicinal Chemistry in 2022.Name: 2-Methoxyethylamine The following contents are mentioned in the article:
The ATM kinase is a key mol. regulating DNA damage response and can be targeted resulting in efficient radio- or chemosensitization. Due to the enormous size of this protein and the associated difficulties in obtaining high-quality crystal structures, we sought to develop an accurate in silico model to identify new targeting possibilities. We identified a urea group as the most beneficial chem. anchor point, which could undergo multiple interactions in the aspartate-rich hydrophobic region I of the atypical ATM kinase domain. Based on in silico data, we designed and synthesized a comprehensive set of novel urea-based inhibitors and characterized them in diverse biochem. assays. Using this strategy, we identified inhibitors with subnanomolar potency, which were further evaluated in cellular models, selectivity and early DMPK properties. Finally, the two lead compounds 34 and 39 exhibited subnanomolar cellular activity along with an excellent selectivity profile and favorable metabolic stability. This study involved multiple reactions and reactants, such as 2-Methoxyethylamine (cas: 109-85-3Name: 2-Methoxyethylamine).
2-Methoxyethylamine (cas: 109-85-3) belongs to ethers. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits. Liquid esters of low volatility serve as softening agents for resins and plastics. Esters also include many industrially important polymers. Polymethyl methacrylate is a glass substitute sold under the names Lucite and Plexiglas; polyethylene terephthalate is used as a film (Mylar) and as textile fibres sold as Terylene, Fortrel, and Dacron.Name: 2-Methoxyethylamine
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem