93614-80-3Relevant articles and documents
Preparation method of alpha-deuterated olefine aldehyde
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Paragraph 0026; 0097-0100; 0113; 0114, (2022/03/27)
The invention relates to a preparation method of alpha-deuterated olefine aldehyde, which comprises the following steps: by taking alpha, beta-olefine aldehyde as a raw material, carrying out a reversible Michael addition mechanism under the action of deuterium water, a nucleophilic reagent and an organic catalyst to obtain an alpha-deuterated olefine aldehyde compound. The method has high selectivity, and does not generate deuterated by-products at other positions. The alpha-deuterated olefine aldehyde compound prepared by the invention has great application value, can be further widely converted to prepare mono (poly) deuterated olefin and derivatives, olefine acid, conjugated olefine aldehyde, eneyne and other compounds, and has important significance in drug synthesis.
Method for preparing olefine aldehyde by catalyzing terminal alkyne or terminal conjugated eneyne and diphosphine ligand used in method
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Paragraph 0140-0145, (2021/05/29)
The invention discloses a method for preparing olefine aldehyde by catalyzing terminal alkyne or terminal conjugated eneyne and a diphosphine ligand used in the method. According to the invention, indole-substituted phosphoramidite diphosphine ligand which is stable in air and insensitive to light is synthesized by utilizing a continuous one-pot method, and the indole-substituted phosphoramidite diphosphine ligand and a rhodium catalyst are used for jointly catalyzing to successfully achieve a hydroformylation reaction of aromatic terminal alkyne and terminal conjugated eneyne under the condition of synthesis gas for the first time, so that an olefine aldehyde structure compound can be rapidly and massively prepared, and particularly, a polyolefine aldehyde structure compound which is more difficult to synthesize in the prior art can be easily prepared and synthesized, and a novel method is provided for synthesis and modification of drug molecules, intermediates and chemical products.
Potent Inhibition of Nicotinamide N-Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics
Buijs, Ned,Campagna, Roberto,Emanuelli, Monica,Gao, Yongzhi,Innocenti, Paolo,Jespers, Willem,Martin, Nathaniel I.,Parsons, Richard B.,Sartini, Davide,Van Haren, Matthijs J.,Van Westen, Gerard J. P.,Zhang, Yurui,Gutiérrez-De-Terán, Hugo
, p. 12938 - 12963 (2021/09/11)
Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, with the most potent inhibitors sharing structural features based on elements of the nicotinamide substrate and the S-adenosyl-l-methionine (SAM) cofactor. We here report the development of new bisubstrate inhibitors that include electron-deficient aromatic groups to mimic the nicotinamide moiety. In addition, a trans-alkene linker was found to be optimal for connecting the substrate and cofactor mimics in these inhibitors. The most potent NNMT inhibitor identified exhibits an IC50 value of 3.7 nM, placing it among the most active NNMT inhibitors reported to date. Complementary analytical techniques, modeling studies, and cell-based assays provide insights into the binding mode, affinity, and selectivity of these inhibitors.