638-44-8

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General Description

N,N'-(dithiodiethylene)bisacetamide, also known as Bismate or Bis(2-acetamido-2-carboxyethyl) disulfide, is a chemical compound with the molecular formula C8H14N2O4S2. It is a water-soluble substance that is commonly used as a crosslinking agent in polymer chemistry and as a vulcanizing agent in rubber production. Its unique structure allows it to form strong covalent bonds between polymer chains, improving the strength, elasticity, and durability of various materials. Bismate is also used in the synthesis of pharmaceuticals, particularly as a reagent in the production of antibiotics and other medicinal compounds. Additionally, it has potential applications in the development of adhesives, coatings, and other advanced materials. However, it is important to handle this chemical with care, as it can be harmful if inhaled, ingested, or absorbed through the skin.

Upstream product

• 56-17-7 cystamine dihydrochioride 
• 108-24-7 acetic anhydride 
• 42963-36-0 4,6-dimethyl-<1,2,5>oxadiazolo<3,4-d>pyrimidine-5,7(4H,6H)-dione 1-oxide 
• 1190-73-4 2-(acetylamino)ethanethiol 
• 166667-90-9 S-nitroso-N-acetylcysteamine 
• 7652-46-2 Ac-Cys-OMe 
• 111807-83-1 4-(3-tert-butyldimethylsilyloxyphenyl)-4-methoxyspiro<1,2-dioxetane-3,2'-adamantane> 
• 156-57-0 2-mercaptoethylamine hydrochloride 
• 13265-60-6 S-(2-acetylaminoethyl) dimethyl phosphorodithioate 
• 10048-08-5 2-Acetamidoaethyl-N,N-dimethyl-trithiopercarbamat 
• 151-56-4 ethyleneimine 
• 507-09-5 tiolacetic acid 
• 51-85-4 2,2'-dithio-bis[ethylamine] 

Downstream Products

• 25116-54-5 N-(2-Acetamidoethylthio)-p-toluolsulfonamid 
• 1420-88-8 S-[2-(acetylamino)ethyl] ethanethioate 
• 1536201-91-8 C₁₀H₁₂N₂O₅S₂ 
• 25116-48-7 4-(2-Acetylamino-ethylsulfanylamino)-benzoic acid methyl ester 
• 1190-73-4 2-(acetylamino)ethanethiol 

Relevant academic research and scientific papers

Oxidative Formation of Disulfide Bonds by a Chemiluminescent 1,2-Dioxetane under Mild Conditions

The oxidation of alkyl thiols to disulfides has been achieved under mild conditions using a chemiluminescent 1,2-dioxetane as a stoichiometric oxidant. Besides the mild and biocompatible reaction conditions, this approach offers the possibility to monitor the presence of thiols through oxidation and chemiluminescence of the remaining dioxetane.

Characterization of the promiscuous: N-Acyl CoA transferase, LgoC, in legonoxamine biosynthesis

More than 500 siderophores are known to date, but only three were identified to be aryl-containing hydroxamate siderophores, legonoxamines A and B from Streptomyces sp. MA37, and aryl ferrioxamine 2 from Micrococcus luteus KLE1011. Siderophores are produced by microorganisms to scavenge iron from the environment, thereby making this essential metal nutrient available to the microbe. We demonstrate here that LgoC from MA37 is responsible for the key aryl-hydroxamate forming step in legonoxamine biosynthesis. Biochemical characterization established that LgoC displays considerable promiscuity for the acylation between N-hydroxy-cadaverine and SNAC (N-Acetylcysteamines) thioester derivatives.

Step-Economic Synthesis of Biomimetic β-Ketopolyene Thioesters and Demonstration of Their Usefulness in Enzymatic Biosynthesis Studies

Studies on the biosynthetic processing of polyene thioester intermediates are complicated by limited access to appropriate substrate surrogates. We present a step-economic synthetic access to biomimetic β-ketopolyene thioesters that is based on an Ir-catalyzed reductive Horner-Wadsworth-Emmons olefination. New β-ketotriene and pentaenethioates of pantetheine and N-acetylcysteamine were exemplarily synthesized via short and concise routes. The usefulness of these compounds was demonstrated in an in vitro assay with the ketoreductase domain MycKRB from mycolactone biosynthesis.

METFORMIN DERIVATIVES

The present invention relates to novel biguanide derivatives including their pharmaceutically acceptable salts. The invention also relates processes for the preparation of, intermediates used in the preparation of, pharmaceutical compositions containing and the uses of such compounds in treating disorders such as diabetes.

CHIRAL CONTROL

The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same.

Reaction of ascorbic acid with S-nitrosothiols: Clear evidence for two distinct reaction pathways

Ascorbate reacts with S-nitrosothiols generally, in the pH range 3-13 by way of two distinct pathways, (a) at low [ascorbate], typically below ～1 × 10-4 mol dm-3 which leads to the formation of NO and the disulfide, and (b) at higher [ascorbate] when the products are the thiol and NO. Reaction (a) is Cu2+-dependent, and is completely cut out in the presence of EDTA, whereas reaction (b) is totally independent of [Cu2+] and takes place readily whether EDTA is present or not. For S-nitrosoglutathione (GSNO) the two reactions can be made quite separate, although for some reactants the two reactions overlap. In reaction (a), ascorbate acts as a reducing agent, generating Cu+ from Cu2+, which in turn reacts with RSNO forming initially NO, Cu2+ and RS-. The latter can then play the role of reducing agent for Cu2+, leading to disulfide formation. Ascorbate will initiate reaction when the free thiolate has initially been reduced to a very low level by the synthesis of RSNO from a large excess of nitrous acid over the thiol. Reaction (b) is interpreted in terms of nucleophilic attack by ascorbate at the nitroso-nitrogen atom, leading to thiol and O-nitrosoascorbate which breaks up, by a free-radical pathway, to give dehydroascorbic acid and NO. A similar pathway is the accepted mechanism in the literature for the nitrosation of ascorbate by nitrous acid and alkyl nitrites. The rate constant for the Cu2+-independent pathway increases sharply with pH and analysis of the variation of the rate constant with pH identifies a reaction pathway via both the mono- and di-anion forms of ascorbate, with the latter being the more reactive. As expected the entropy of activation is large and negative. Some aspects of structure-reactivity trends are discussed.

Facile synthesis and NO-generating property of 4H-[1, 2, 5]oxadiazolo[3, 4-d]pyrimidine-5, 7-dione 1-oxides

4H-[1, 2, 5]Oxadiazolo[3, 4-d]pyrimidine-5, 7-dione 1-oxides (2) are conveniently prepared in high yields by the oxidative intramolecular cyclization of 6-amino-5-mtro-lH-pyrimidine-2, 4-diones (1) employing iodosylbenzene diacetate as an oxidant in the presence of lithium hydride. The generation of nitric oxide (NO) and NO-related species from 2 occurs in the presence of thiols such as AT-acetylcysteamine, cysteine, and glutathione under physiological conditions. The evidence for the NO generation derives from mechanistic interpretations for the reaction of 2 with thiols and other chemical observations.

Lipophilic analogues of sparsomycin as strong inhibitors of protein synthesis and tumor growth: A structure-activity relationship study

Fourteen derivatives of sparsomycin (1) were synthesized. Six of them were prepared following a novel synthetic route starting from the L-amino acid alanine. Some physicochemical properties, viz. lipophilicity and water solubility, of selected derivatives were measured. The biological activity was tested in vitro in cell-free protein synthesis inhibition assays, in bacterial and tumor cell growth inhibition assays, and in the L1210 leukemia in vivo model in mice. Also for selected drugs the acute toxicity in mice was determined. Ribosomes from both an eukaryotic and a prokaryotic organism were used in the protein synthesis inhibition systems. A linear correlation between the lipophilicity parameters measured was observed. Water solubility and drug toxicity in mice were found to be linearly correlated with lipophilicity. All the derivatives studied are more lipophilic than 1. The deshydroxysparsomycin analogues (30-33) showed an interesting phenomenon: increase in hydrophobicity was accompanied by a considerable increase in water solubility. We found that an increase in hydrophobicity of the drug as a result of replacing the SMe group of 1 with larger alkylthio groups causes an increase in the biological activity of the drug. However, not only the hydrophobicity but also shape and size of the substituent are important; in the homologous series 1-9-10-11-12, 21-22-23-24, and 30-31-32-33, highest protein synthesis inhibitory and in vitro cytostatic activity is found with compounds 11, 23, and 32, respectively, and in comparison with the highly active n-butyl compound 10, the isomeric tert-butyl compound 13 is rather inactive. Polar substituents replacing the SMe group, i.e. Cl in 17 and 35, also render the molecule inactive. Substituting the bivalent sulfur atom for a methylene group decreases the drug's activity. This effect can be compensated for by increasing the length of the alkylsulfinyl side chain. The agreement between the results derived from cell-free and 'in vivo' tests is good. The assays using ribosomes of bacterial and eukaryotic organisms give similar results although the latter seem to be more sensitive to changes in hydrophobicity of the drug. Our results confirm the presence of a hydrophobic region at the peptidyl transferase center of the ribosome; the interaction of sparsomycin with this region is more pronounced in the eukaryotic particles. The sparsomycin analogues 11, 23, and 30 show the highest antitumor activity against L1210 leukemia in mice, their median T/C values are 386, 330, and 216%, respectively. Sparsomycin (1), showing a T/C value of 117%, is only marginally active against this tumor. The analogues tested are 5-100 times less toxic than 1.

Transformation of DAEP under Various Oxidative Conditions

14C-DAEP was subjected to four different oxidative conditions, and the products were identified.On peracid oxidation in dichloromethane, DAEP gave the oxon (1) predominantly, and 2-acetylaminoethyl dimethoxyphosphinyl disulphide (3), N-acetylcysteamine (10), its oxidized dimer (11) and a further oxidation product of compound (11).This indicates that an unstable phosphorus oxythionate was initially formed, which lost sulfur, was rearranged, and hydrolyzed to give these products.Under other conditions, phosphinyl disulfide 3 was not found.DAEP was metabolized in vitro with a rat liver microsome-NADPH system via oxydation.The aqueous reaction condition prevented the formation of compound 3 from the intermediate, which predominated as well as the oxon formation under anhydrous or close conditions.The formation of various products with sunlight irradiation on glass plates or on bean leaves could be interpreted by oxidation at P=S, C1 and C2 positions, demethylation, and deacetylation, followed by further transformation.The initial formation of phosphorus oxythionate seems to play an important role in the oxidation of the organothionophosphorus compound.

Rate Constants and Equilibrium Constants for Thiol-Disulphide Interchange Reactions Involving Oxidized Glutathione

The rate of reduction of oxidized glutathione (GSSG) to glutathione (GSH) by thiolate (RS-) follows a Broensted relation in pKas of the conjugate thiols (RSH): βnuc ca. 0.5.This value is similar to that for reduction of Ellman's reagent: βnuc ca. 0.4 - 0.5.Analysis of a number of rate and equilibrium data, taken both from this work and from the literature, indicates that rate constants, k, for a range of thiolate-disulphide interchange reactions are correlated well by equations of the form log k = C + βnucpKanuc + βcpKac + βlgpKalg ( nuc = nucleophile, c = central, and lg = leaving group sulfur): eq 36 - 38 give representative values of the Broensted coefficients.The values of these Bronsted coefficients are not sharply defined by the available experimental data, although eq 36 - 38 provide useful kinetic models for rates of thiolate-disulfide interchange reactions.The uncertainty in these parameters is such that their detailed mechanistic interpretation is not worthwhile, but their qualitative interpretation - that all three sulphur atoms experience a significant effective negative charge in the transition state, but that the charge is concentrated on the terminal sulfurs - is justified.Equilibrium constants for reduction of GSSG using α,ω-dithiols have been measured.The reducing potential of the dithiol is strongly influenced by the size of the cyclic disulfide formed on its oxidation: the most strongly reducing dithiols are those which can form six-membered cyclic disulfides.Separate equilibrium constants for thiolate anion-disulphide interchange (KS-) and for thiol-disufide interchange (KSH) have been estimated from literature data: KS- is roughly proportional to 2ΔpKa is the difference between the pKas of the two thiols involved in the interchange.The contributions of thiol pKa values to the observed equilibrium constants for reduction of GSSG with α,ω-dithiols appear to be much smaller than those ascribable to the influence of structure on intramolecular ring formation.These equilibrium and rate constants are helpful in choosing dithiols for use as antioxidants in solutions containing proteines: dithiothreitol (DTT), 1,3-dimercapto-2-propanol (DMP), and 2-mercaptoethanol have especially useful properties.