31618-90-3Relevant articles and documents
Monosubstituted pillar[5]arene functionalized with (amino)phosphonate fragments are "smart" building blocks for constructing nanosized structures with some s-and p-metal cations in the organic phase
Nazarova, Anastasia A.,Yakimova, Luidmila S.,Padnya, Pavel L.,Evtugyn, Vladimir G.,Osin, Yuri N.,Cragg, Peter J.,Stoikov, Ivan I.
, p. 14450 - 14458 (2019)
Monosubstituted pillar[5]arenes containing a phosphonate fragment were successfully obtained in good yields. It was found that the introduction of bulky fragments containing tetra-coordinated pentavalent phosphorus atoms prevents self-Assembly of monosubstituted pillar[5]arenes and the formation of supramolecular polymers. Pillar[5]arenes with phosphonate and 1-Aminophosphonate substituents demonstrated recognition towards Na+, K+, Cs+ and Pb2+. Their ability to form complexes with these cations was evaluated by UV spectroscopy. Dynamic light scattering (DLS) revealed the formation of aggregates with K+, Cs+ and Pb2+. It was established that the substituent at the α-carbon atom of the aminophosphonate fragment played a significant role in Pb2+ binding. DLS and transmission electron microscopy revealed that Pb2+-induced aggregation formed particles with a monodisperse distribution of 0.02-0.23 and a hydrodynamic diameter of 58-178 nm.
Development and optimization of halogenated vinyl sulfones as Nrf2 activators for the treatment of Parkinson's disease
Choi, Ji Won,Kim, Siwon,Yoo, Jong Seok,Kim, Hyeon Jeong,Kim, Hyeon Ji,Kim, Byung Eun,Lee, Elijah Hwejin,Lee, Yong Sup,Park, Jong-Hyun,Park, Ki Duk
supporting information, (2021/01/06)
The Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays a pivotal role in the cellular defense system against oxidative stress by inducing antioxidant and anti-inflammatory effects. We previously developed Nrf2 activators that potentially protect the death of dopaminergic (DAergic) neuronal cells against oxidative stress in Parkinson's disease (PD). In this study, we designed and synthesized a class of halogenated vinyl sulfones by inserting halogens and pyridine to maximize Nrf2 activation efficacy. Among the synthesized compounds, (E)-3-chloro-2-(2-((2-chlorophenyl)sulfonyl)vinyl)pyridine (9d) significantly exhibited potent Nrf2 activating efficacy (9d: EC50 = 26 nM) at least 10-fold compared with the previous developed compounds (1 and 2). Furthermore, treating with 9d remarkably increased Nrf2 nuclear translocation and Nrf2 protein levels in microglial BV-2 cells. 9d was shown to induce the expression of antioxidant response genes HO-1, GCLC, GCLM, and SOD-1 at both the mRNA and protein levels and suppress proinflammatory cytokines and enzymes. Also, 9d remarkably protected DAergic neurons and restored the PD-associated motor dysfunction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model.
NOVEL HALO-(3-(PHENYLSULFONYL)PROP-1-ENYL)PYRIDINE DERIVATIVE AND USE THEREOF
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Paragraph 0060-0061, (2021/06/25)
The present invention relates to a novel halo-(3-(phenylsulfonyl)prop-1-enyl)pyridine derivative or a pharmaceutically acceptable salt thereof; a preparation method thereof; and an Nrf2 activator and a pharmaceutical composition for preventing or treating diseases induced by a decrease in Nrf2 activity, both of which comprise the same as an active ingredient.
Asymmetric Synthesis of Chiral 1,3-Disubstituted Allylsilanes via Copper(I)-Catalyzed 1,4-Conjugate Silylation of α,β-Unsaturated Sulfones and Subsequent Julia-Kocienski Olefination
Jia, Xue-Shun,Wang, Xian-Liang,Xiao, Jun-Zhao,Yin, Liang,Yin, Xing-Hao
, p. 1916 - 1922 (2021/06/07)
A general synthesis of chiral 1,3-disubstituted allylsilanes is established through copper(I)-catalyzed asymmetric 1,4-conjugate silylation of α,β-unsaturated sulfones and subsequent Julia-Kocienski olefination. By modification of McQuade's NHC ligand, the catalytic asymmetric conjugate silylation with a broad substrate scope is achieved in high enantioselectivity. The following Julia-Kocienski olefination proceeds smoothly at room temperature to deliver an array of chiral allylsilanes in moderate yields. More interestingly, a one-pot asymmetric synthesis with high synthetic efficiency is successfully realized. Utility of the prepared chiral 1,3-disubsituted allylsilanes is demonstrated in the asymmetric allylation of both aldehyde and aldimine. Finally, an interesting “match and mismatch” phenomenon is observed in the asymmetric allylation of chiral aldehydes.
Preparation method of diethyl p-toluenesulfonyloxymethylphosphonate
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Paragraph 0092-0094; 0097-0106; 0110-0115; 0119-0125, (2021/07/17)
The invention relates to a preparation method of diethyl p-toluenesulfonyloxymethylphosphonate. The method comprises the following steps of under the protection of nitrogen, adding diethyl phosphite into a reaction container, then sequentially adding carbonate and tetrabutylammonium bromide, and dropwise adding a formaldehyde aqueous solution while stirring, continuously adding the carbonate and the formaldehyde aqueous solution in batches, after the reaction endpoint is reached, adding methylbenzene, adding paratoluensulfonyl chloride while stirring, and reacting, dropwise adding an alkali solution, after dropwise adding, keeping the temperature until the reaction end point, and standing, separating liquid, placing an upper-layer organic phase for later use, and extracting a lower-layer water phase with methylbenzene, and combining the two organic phases, adding a sodium chloride aqueous solution for washing, and concentrating an organic layer under reduced pressure to obtain a liquid product. Energy consumption does not need to be additionally increased in the reaction, so that frozen saline water required for cooling in the traditional process is abandoned, and the energy consumption is greatly reduced; compared with the traditional process with the step of about 85% of the yield, the yield is improved by 10-15%, the economic value of the product is greatly improved, and environmental protection is facilitated.
Isomerisation of Vinyl Sulfones for the Stereoselective Synthesis of Vinyl Azides
Collins, Niall,Connon, Robert,Evans, Paul,Sánchez-Sanz, Goar
supporting information, p. 6228 - 6235 (2020/10/02)
Reported is the construction, and facile base-mediated conversation of ten differently substituted 3-azido E-vinyl sulfones (γ-azido-α,β-unsaturated sulfones) into their isomeric vinyl azide counterparts. The requisite 3-azido E-vinyl sulfones were prepared from 3-bromo E-vinyl sulfones, which in turn were accessed from allyl sulfones via a bromination-elimination sequence. In relation to this a one-pot azidation-isomerisation sequence was developed which enabled the direct formation of the vinyl azides from the corresponding 3-bromo E-vinyl sulfones. Similarly, a convenient one-pot Horner–Wadsworth–Emmons olefination-isomerisation approach was utilised in order to prepare some of the allylic sulfones used in this study. The vinyl azide forming process typically proceeded with high levels of Z-selectivity, although this was dependent on the vinyl sulfone substitution pattern. Thus, with either no substituent or a methyl group in the γ- or β-position, relative to the sulfone, good, to high levels of Z-selectivity (Z/E = 85:15 to ≥ 95:5) were obtained. However, incorporation of an α-sulfonyl methyl substituent led to an E-selective process (Z/E = 20:80). A non-bonding interaction between the azido group and the α-sulfonyl vinylic proton is proposed, which acts as a conformational control mechanism to help guide the stereochemical outcome.
MONOMER AND MULTIMERIC ANTI-HBV AGENTS
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Page/Page column 143; 184, (2020/05/15)
The present invention is directed to compounds, compositions and methods for preventing, treating or curing hepatitis B (HBV) infection in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment, prevention or eradication of HBV infection.
Method for recycling byproduct p-toluene magnesium sulfonate to synthesize tenofovir
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Paragraph 0033; 0034, (2019/10/01)
The invention relates to the technical field of medicine chemicals and in particular discloses a method for recycling a byproduct p-toluene magnesium sulfonate to synthesize tenofovir. According to the method, hydroxymethylphosphonic acid diethyl ester and paratoluensulfonyl chloride are adopted as raw materials, magnesium carbonate is adopted as an acid-binding agent, p-toluenesulfonyl oxymethyldiethyl phosphate is synthesized, tenofovir is synthesized from the p-toluenesulfonyl oxymethyl diethyl phosphate and R-9-(2-hydroxypropyl), and meanwhile, a byproduct p-toluene magnesium sulfonate isgenerated; and magnesium carbonate and sodium p-toluenesulfonate are generated through a reaction of the p-toluene magnesium sulfonate and sodium carbonate. According to the method, the byproduct p-toluene magnesium sulfonate is mainly recycled, process treatment difficulties are reduced, byproducts p-toluene magnesium sulfonate and magnesium chloride which are obtained after treatment are high in purity, export sales can be achieved, the magnesium carbonate can be applied to synthesis of the p-toluenesulfonyl oxymethyl diethyl phosphate, and the production cost can be reduced.
Optimization of Vinyl Sulfone Derivatives as Potent Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators for Parkinson's Disease Therapy
Choi, Ji Won,Kim, Siwon,Park, Jong-Hyun,Kim, Hyeon Jeong,Shin, Su Jeong,Kim, Jin Woo,Woo, Seo Yeon,Lee, Changho,Han, Sang Moon,Lee, Jaeick,Pae, Ae Nim,Han, Gyoonhee,Park, Ki Duk
supporting information, p. 811 - 830 (2019/01/08)
We previously developed a novel series of vinyl sulfones as nuclear factor erythroid 2-related factor 2 (Nrf2) activators with therapeutic potential for Parkinson's disease (PD). However, the previously developed lead compound (1) exhibited undesirable druglike properties. Here, we optimized vinyl sulfones by introducing nitrogen heterocycles to improve druglike properties. Among the synthesized compounds, 17e was the most promising drug candidate with good druglike properties. Compound 17e showed superior effects on Nrf2 activation in cell-based assays compared to compound 1 (17e: half-maximal effective concentration (EC50) = 346 nM; 1: EC50 = 530 nM). Compound 17e was further confirmed to induce expression of Nrf2-dependent antioxidant enzymes at both mRNA and protein levels. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD, 17e significantly attenuated loss of tyrosine hydroxylase-immunopositive dopaminergic neurons, suppressed microglial activation, and alleviated PD-associated motor dysfunction. Thus, 17e is a novel Nrf2 activator with excellent druglike properties and represents a potential therapeutic candidate for PD.
A synthetic paratoluene sulfonyl oxygen methyl phosphine acid ethyl ester
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Paragraph 0033; 0035; 0047; 0049; 0050; 0052; 0053; 0055, (2019/01/08)
The invention discloses a method for synthesizing paratoluene sulfonyl oxygen methyl phosphine acid ethyl ester method, 37% formaldehyde aqueous solution and the catalyst mixing, the dropping of the diethyl phosphite, the completion of the dropping, thermal insulation reaction 2 hours, to the reaction solution, the reaction solution into the solvent, to the toluene sulfonyl chloride, low temperature instillment base, the dropwise insulation 2 hours, extraction, washing, distillation, the surplus materials is high-purity paratoluene sulfonyl oxygen methyl phosphine acid diethyl ester. The method of the invention solve the existing craft in the low purity, yield is not high, the process is complicated, trouble in processing after, environmental pressure, is not suitable for industrial and the like.
