In 2016,Jordan, John B.; Whittington, Douglas A.; Bartberger, Michael D.; Sickmier, E. Allen; Chen, Kui; Cheng, Yuan; Judd, Ted published 《Fragment-Linking Approach Using 19F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of β-Secretase》.Journal of Medicinal Chemistry published the findings.Application In Synthesis of 6-Bromopyridin-3-amine The information in the text is summarized as follows:
Fragment-based drug discovery (FBDD) has become a widely used tool in small-mol. drug discovery efforts. One of the most commonly used biophys. methods in detecting weak binding of fragments is NMR (NMR) spectroscopy. In particular, FBDD performed with 19F NMR-based methods has been shown to provide several advantages over 1H NMR using traditional magnetization-transfer and/or two-dimensional methods. Here, we demonstrate the utility and power of 19F-based fragment screening by detailing the identification of a second-site fragment through 19F NMR screening that binds to a specific pocket of the aspartic acid protease, β-secretase (BACE-1). The identification of this second-site fragment allowed the undertaking of a fragment-linking approach, which ultimately yielded a mol. exhibiting a more than 360-fold increase in potency while maintaining reasonable ligand efficiency and gaining much improved selectivity over cathepsin-D (CatD). X-ray crystallog. studies of the mols. demonstrated that the linked fragments exhibited binding modes consistent with those predicted from the targeted screening approach, through-space NMR data, and mol. modeling.6-Bromopyridin-3-amine(cas: 13534-97-9Application In Synthesis of 6-Bromopyridin-3-amine) was used in this study.
6-Bromopyridin-3-amine(cas: 13534-97-9) belongs to anime. The methylamines occur in small amounts in some plants. Many polyfunctional amines (i.e., those having other functional groups in the molecule) occur as alkaloids in plants—for example, mescaline, 2-(3,4,5-trimethoxyphenyl)ethylamine; the cyclic amines nicotine, atropine, morphine, and cocaine; and the quaternary salt choline, N-(2-hydroxyethyl)trimethylammonium chloride, which is present in nerve synapses and in plant and animal cells.Application In Synthesis of 6-Bromopyridin-3-amine