- Bivalent SIRT1 inhibitors
-
In the current study, bivalent compounds 1–17 constructed by covalently linking the ?-amino group of lysine in a tripeptidic scaffold to a functionality via a linker were prepared and examined for their inhibitory potencies against SIRT1, a prototypical member of the β-nicotinamide adenine dinucleotide (β-NAD+)-dependent sirtuin family of protein Nε-acyl-lysine deacylases. A few of them were found to be stronger SIRT1 inhibitors than the N?-acetyl-lysine-containing monovalent counterparts 18 and 19. As exemplified with compounds 6 and 18, a bivalent SIRT1 inhibitor could exhibit a greater degree of inhibitory selectivity among SIRT1/2/3 than the corresponding monovalent counterpart. This study has laid a foundation for the future development of superior bivalent inhibitors against the (patho)physiologically and therapeutically important sirtuin family of deacylase enzymes.
- Wang, Juan,Zang, Wenwen,Liu, Jiajia,Zheng, Weiping
-
-
Read Online
- Co-production method of thionocarbamate and benzyl thioether acetic acid and application of the method
-
The invention discloses a co-production method of thionocarbamate and benzyl thioether acetic acid and application of the method. The method comprises the following steps: with xanthate and benzyl chloride as initial raw materials, and performing esterification reaction to obtain benzyl xanthate; carrying out ammonolysis on benzyl xanthate by using primary amine to obtain thionocarbamate and benzyl mercaptan; further adding sodium chloroacetate into the mixture for reaction, thus generating benzyl thioether sodium acetate; finally, performing liquid separation to obtain the thionocarbamate collecting agent and a water phase containing benzyl thioether sodium acetate. The benzyl thioether sodium acetate-containing water phase can further react with benzyl chloride to obtain benzyl thioetherbenzyl acetate or be acidified and esterified with fatty alcohol to generate benzyl thioether alkyl acetate, and the two ester compounds can be subjected to hydroximation to synthesize benzyl thioether ethyl hydroximic acid. The method solves the problems of difficult recovery, difficult utilization and unpleasant smell of the byproduct sulfhydryl compound in the traditional thionocarbamate process, realizes co-production of benzyl thioether acetic acid and derivatives thereof, and improves the reaction efficiency.
- -
-
Paragraph 0081-0082
(2019/12/02)
-
- Method for utilizing byproduct 2-sodium thioglycollate in production process of thionocarbamate
-
The invention belongs to wastewater treatment and in particular discloses a method for utilizing a byproduct 2-sodium thioglycollate in the production process of thionocarbamate. The method comprisesthe following steps: by taking a byproduct 2-sodium thioglycollate in the production process of thionocarbamate as a raw material, enabling the byproduct to react with a halogenation reagent so as toobtain alkyl thioether acetic acid; performing esterification on the alkyl thioether acetic acid with methanol so as to obtain alkyl thioether methyl acetate; and further enabling the alkyl thioethermethyl acetate to react with hydroxylamine hydrochloride, so as to obtain alkyl thioether ethyl hydroximic acid. By adopting the method, the problem that the byproduct 2-sodium thioglycollate in a process of thionocarbamate is hard to recycle can be solved, the utilization rate of the byproduct is increased, and the environment can be protected.
- -
-
Paragraph 0072-0073
(2019/12/25)
-
- Styryl sulfones compound, its preparation method and its use as neuroprotective agents
-
The application relates to design of a novel molecule with ester group substituted by sulfone group by using a caffeic acid phenethyl ester (CAPE) with neuroprotective activity extracted from natural propolis as a primer according to bioisosterism principle and hydrogen-bond interaction theory; and the molecule has a structural general formula I, and the definition of each group is shown in the claims. The invention also relates to compound in vitroantioxidation capability evaluation, neuroprotective activity evaluation on cell level and traverse blood brain barrier ability evaluation. Activity evaluation results show that the synthesized novel compound has enhanced neuroprotective activity and can easily traverse the blood brain barrier, thus becoming a novel neuroprotective agent for treating neurodegenerative diseases.
- -
-
Paragraph 0059-0061
(2018/02/04)
-
- Synthesis of Cyclic α-Diazo-β-keto Sulfoxides in Batch and Continuous Flow
-
Diazo transfer to β-keto sulfoxides to form stable isolable α-diazo-β-keto sulfoxides has been achieved for the first time. Both monocyclic and benzofused ketone derived β-keto sulfoxides were successfully explored as substrates for diazo transfer. Use of continuous flow leads to isolation of the desired compounds in enhanced yields relative to standard batch conditions, with short reaction times, increased safety profile, and potential to scale up.
- McCaw, Patrick G.,Buckley, Naomi M.,Eccles, Kevin S.,Lawrence, Simon E.,Maguire, Anita R.,Collins, Stuart G.
-
p. 3666 - 3679
(2017/04/11)
-
- E-3,4-di-calcium method for preparing vinyl sulfoxide compound thereof as a neuroprotective pharmaceutical application
-
The invention relates to an application of E-3,4-dihydroxyphenylvinyl sulfoxide represented by the formula I in preparation of nerve protection drugs for treating neurodegenerative diseases, wherein the definitions of each group in the formula I are listed in the description. The invention also relates to a preparation method of E-3,4-dihydroxyphenylvinyl sulfoxide.
- -
-
Paragraph 0030-0031
(2017/01/12)
-
- New organic single crystal of (benzylthio)acetic acid: Synthesis, crystal structure, spectroscopic (ATR-FTIR, 1H and 13C NMR) and thermal characterization
-
(Benzylthio)acetic acid (Hbta) was synthesized with 78% yield from benzyl chloride and thiourea as substrates. Well-shaped crystals of Hbta were grown by slow solvent evaporation technique from pure methanol. The compound was investigated by single-crystal X-ray and powder diffraction techniques and was also characterized by other analytical methods, like ATR-FTIR, 1H and 13C NMR and TG/DSC. The acid molecule adopts bent conformation in the solid state. The crystal structure of Hbta is stabilized by numerous intermolecular interactions, including O-H···O, C-H···O, C-H···S and C-H···π contacts. Thermal decomposition of the obtained material takes place above 150 °C.
- Sienkiewicz-Gromiuk, Justyna,Tarasiuk, Bogdan,Mazur, Liliana
-
-
- Synthesis and antioxidant activity of 1,4-[Bis(3-arylmethanesulfonyl pyrrolyl and pyrazolyl)]benzenes
-
A variety of (1,4-phenylene)bis(arylmethanesulfonylpyrroles and pyrazoles) were prepared by the cycloaddition of 1,3-dipolar reagents, tosylmethyl isocyanide and diazomethane to the Michael acceptor, 1,4-bis(E)-2- ((arylmethanesulfonyl)vinyl)benzene. All the compounds were evaluated for antioxidant activity. Amongst the tested compounds, one of them displayed excellent radical scavenging activity in all the three methods evaluated when compared with the standard Ascorbic acid. On the other hand, 1,4-(bis(3-arylmethanesulfonyl)-1H-pyrazol-4-yl)benzenes exhibited comparatively higher antioxidant activity than 1,4-(bis(3-arylmethanesulfonyl)-1H-pyrrol-4- yl) benzenes. In general, it was observed that compounds having methoxy substitutent on aromatic ring displayed greater antioxidant activity than the other substituents. ?2014 Sociedade Brasileira de Qui?mica.
- Lavanya, Gopala,Padmavathi, Venkatapuram,Padmaja, Adivireddy
-
p. 1200 - 1207
(2014/08/05)
-
- Design, synthesis, and biological evaluation of (E)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides as novel multifunctional neuroprotective agents
-
Novel (E)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides were designed and synthesized as new analogues of 1, which showed interesting multifunctional neuroprotective effects, including antioxidative and antineuroinflammatory properties. Specifically, target compounds display excellent potency in scavenging reactive free radicals and demonstrate potent effects against various kinds of toxicities, including H2O2, 6-hydroxydopamine, and lipopolysaccharide in different types of neuronal cells. The antioxidative properties of the target compounds are more potent than that of 1, and the antineuroinflammatory properties are less strong than that of 1. According to the parallel artificial membrane permeation assay for the blood-brain barrier, target compounds possess greater blood-brain barrier (BBB) permeability than 1. In short, due to improvement of the antioxidative effect, stability, and BBB permeability, (E)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides can thus be considered as potential multifunctional neuroprotective agents and serve as new lead candidates in the treatment of neurodegenerative diseases.
- Ning, Xianling,Guo, Ying,Wang, Xiaowei,Ma, Xiaoyan,Tian, Chao,Shi, Xueqi,Zhu, Renzong,Cheng, Can,Du, Yansheng,Ma, Zhizhong,Zhang, Zhili,Liu, Junyi
-
p. 4302 - 4312
(2014/06/09)
-
- Silica-promoted facile synthesis of thioesters and thioethers: A highly efficient, reusable and environmentally safe solid support
-
An efficient, mild and rapid procedure for the acylation and alkylation of aromatic and aliphatic thiols mediated on a silica gel surface at room temperature is described. The protocol allows the protection of thiols under neutral heterogeneous conditions without requiring any bases or Lewis acids, and the silica gel used as the promoter can be recycled for several runs without any loss of activity.
- Basu, Basudeb,Paul, Susmita,Nanda, Ashis K.
-
experimental part
p. 767 - 771
(2010/09/05)
-
- Crystal Structure of 3-(4-Methoxy-benzylidene)-isothiochroman-4-one
-
The title compound, 3-(4-methoxy-benzylidene)-isothiochroman-4-one (C 17H14O2S) was prepared from the reaction of isothiochroman-4-one with benzaldehyde in the presence of small amount of HCl. The structure of the synthesised compound was determined by IR, 1H NMR and X-ray crystallography. The structure was solved in monoclinic, space group P21/n with a = 3.9773 (7) A, b = 10.918 (2) A, c = 30.609 (6) A, β = 90.615 (3)°, V = 1329.1 (4) A3, Z = 4 and with R int = 0.047. The bicyclic ring of isothiochroman-4-one moiety does not adopt a planar geometry. The molecular conformation is stable via C10-H???O1 and C16- H???S1 intramolecular hydrogen-bonding interactions. These contacts involve molecules in an extended two-dimensional sheet to the bc plane.
- Akkurt,YIldIrIm,Kerbal,Bennani,Hadda, T. Ben,Chohan,McKee, Vickie
-
p. 165 - 168
(2011/07/30)
-
- METHODS OF TREATMENT OF AMYLOIDOSIS USING BI-CYCLIC ASPARTYL PROTEASE INHIBITORS
-
The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
- -
-
Page/Page column 193
(2010/02/14)
-
- (E)-styryl sulfone anticancer agents
-
(E)-styryl benzylsulfones of formula I are useful as anticancer agents: wherein R1, R2, R3, and R4 are independently selected from the group consisting of hydrogen, fluoro, chloro, iodo, bromo, C1-C6 alkyl, C1-C4 alkoxy, nitro, cyano and trifluoromethyl, with the proviso that (a) R1, R2 , and R3 not all hydrogen when R4 is 2-chloro or 4-chloro; (b) when R1 and R3 are hydrogen and R2 is 4-bromo or 4-chloro, then R4 may not be 4-chloro, 4-fluoro or 4-bromo; (c) when R1 and R3 are hydrogen and R2 is 4-fluoro, then R4 may not be 4-fluoro or 4-bromo, (d) when R1 is hydrogen, and R4 is 2-fluoro, the R2 and R3 may not be 4-fluoro; and (e) when R1 is hydrogen and R3 is 4-hydrogen, 4-chloro, 4-bromo, 4-methyl or 4-methoxy, and R4 is 2-hydrogen, 2-chloro, or 2-fluoro; then R2 may not be 4-hydrogen, 4-chloro, 4-fluoro, or 4-bromo.
- -
-
-
- Propenyl cephalosporin derivatives and process for the manufacture thereof
-
Disclosed are cephalosporin derivatives of the general formula wherein R is an organic residue with a molecular weight not exceeding 400 bonded to the adjacent sulphur atom via carbon and consisting of carbon, hydrogen, and optional oxygen, sulfur, nitrogen and/or halogen atoms; R1 is hydrogen, lower alkyl or phenyl; and A is a secondary, tertiary or quaternary nitrogen atom bound directly to the propenyl group and being substituted by an organic residue with a molecular weight not exceeding 400 and consisting of carbon, hydrogen, and optional oxygen, sulfur, nitrogen and/or halogen atoms,as well as readily hydrolyzable esters thereof, pharmaceutically acceptable salts of said compounds and hydrates of the compounds of formula I and of their esters and salts.
- -
-
-
- Sulfonyl Esters. V. A Preparation of Dichloromethyl Sulfones
-
α-Sulfonyl methyl esters have been chlorinated in the presence of base.Chlorination proceeds with accompanying demethoxycarbonylation to furnish dichloromethyl sulfones in good yields.
- Langler, Richard Francis,Steeves, Jennifer Lea
-
p. 1641 - 1646
(2007/10/02)
-
- Mass Spectrometry of 2-Alkylthio-2-methylpropanoic Acids and Their Esters and Amides. Structural and Steric Effects on the McLafferty Rearrangement
-
The electron ionization mass spectra (MS) of S-methylated derivatives of N-(2-mercapto-2-methylpropanoyl)-L-cysteine and 2-alkylthio-2-methylpropanoic acids, as well as their esters and amides, were examined.Use of the deuterium labeling technique and accurate mass measurement supported the proposed fragmentation pathways.Extensive loss of CH2S from a molecular ion by the McLafferty rearrangementof a primary hydrogen is important in the MS of S-methyl compounds of amide derivatives.It was demonstrated that the intensity of the rearrangement ion decreases in the order of amide, ester, and acid, and in the case if amides the reaarangement is suppressed by the nonbonded interaction between methyl groups on the α carbon and the amide nitrogen.Keywords-N-(2-mercapto-2-methylpropanoyl)-L-cysteine; 2-alkylthio-2-methylpropanoic acid and methyl ester; 2-alkylthio-2-methylpropanamide; electron impact mass spectrometry; McLafferty rearrangement; steric interaction
- Mori, Yuji,Fujiwara, Shigeru,Miyachi, Toshiko,Kitanishi, Hiroyuki,Oya, Masayuki,et al.
-
p. 1505 - 1517
(2007/10/02)
-
