4439-53-6Relevant articles and documents
The 3F Library: Fluorinated Fsp3-Rich Fragments for Expeditious 19F NMR Based Screening
Troelsen, Nikolaj S.,Shanina, Elena,Gonzalez-Romero, Diego,Danková, Daniela,Jensen, Ida S. A.,?niady, Katarzyna J.,Nami, Faranak,Zhang, Hengxi,Rademacher, Christoph,Cuenda, Ana,Gotfredsen, Charlotte H.,Clausen, Mads H.
, p. 2204 - 2210 (2020)
Fragment-based drug discovery (FBDD) is a popular method in academia and the pharmaceutical industry for the discovery of early lead candidates. Despite its wide-spread use, the approach still suffers from laborious screening workflows and a limited diversity in the fragments applied. Presented here is the design, synthesis, and biological evaluation of the first fragment library specifically tailored to tackle both these challenges. The 3F library of 115 fluorinated, Fsp3-rich fragments is shape diverse and natural-product-like with desirable physicochemical properties. The library is perfectly suited for rapid and efficient screening by NMR spectroscopy in a two-stage workflow of 19F NMR and subsequent 1H NMR methods. Hits against four diverse protein targets are widely distributed among the fragment scaffolds in the 3F library and a 67 % validation rate was achieved using secondary assays. This collection is the first synthetic fragment library tailor-made for 19F NMR screening and the results demonstrate that the approach should find broad application in the FBDD community.
Switching Selectivity in Copper-Catalyzed Transfer Hydrogenation of Nitriles to Primary Amine-Boranes and Secondary Amines under Mild Conditions
Song, Hao,Xiao, Yao,Zhang, Zhuohua,Xiong, Wanjin,Wang, Ren,Guo, Liangcheng,Zhou, Taigang
, p. 790 - 800 (2022/01/11)
A simple and efficient copper-catalyzed selective transfer hydrogenation of nitriles to primary amine-boranes and secondary amines with an oxazaborolidine-BH3 complex is reported. The selectivity control was achieved under mild conditions by switching the solvent and the copper catalysts. More than 30 primary amine-boranes and 40 secondary amines were synthesized via this strategy in high selectivity and yields of up to 95%. The strategy was applied to the synthesis of 15N labeled in 89% yield.
Sulfated polyborate: A dual catalyst for the reductive amination of aldehydes and ketones by NaBH4
Ganwir, Prerna,Chaturbhuj, Ganesh
supporting information, (2021/05/19)
An efficient, quick, and environment-friendly one-pot reductive amination of aldehydes or ketones was developed. In ethanol at 70 °C, a imination catalyzed by sulfated polyborate and further reduced by sodium borohydride yields various amines. The present method has many significant benefits, including a shorter reaction time, excellent yields, and a hassle-free, straightforward experimental process. The reaction has a wide range of applications due to its flexibility, including secondary amine for reductive amination.
Preparation of HIF-2alpha small-molecule inhibitor and application thereof
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Paragraph 0099; 0105, (2021/06/22)
The invention belongs to the technical field of medicines, and relates to an HIF-2 alpha small-molecule inhibitor as well as a preparation method and an application thereof. The HIF-2alpha small-molecule inhibitor is a compound as shown in a structural general formula I and a stereoisomer, a pharmaceutically acceptable salt, a hydrate, a solvate or a prodrug thereof. According to the invention, molecular simulation drug design software MOE is used for screening and molecular docking of pharmacophores, according to a final docking dominant structure and an isosteric principle, a series of compounds are designed and synthesized, and an in-vitro anti-tumor activity screening test shows that the compounds have anti-tumor activity. The HIF-2 alpha small-molecule inhibitor provided by the invention has a relatively good application prospect in the aspect of preventing or treating cancers, particularly glioma.
