- Continuous-flow step-economical synthesis of thiuram disulfidesviavisible-light photocatalytic aerobic oxidation
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A continuous-flow photocatalytic synthesis of the industrially important thiuram disulfides has been developed, utilizing O2as the oxidant and Eosin Y as the photoredox catalyst. This highly atom- and step-economical method features much reduced reaction time as well as excellent product yield and purity, making it a sustainable and potentially scalable process for industrial production.
- Xu, Hao-Xing,Zhao, Ze-Run,Patehebieke, Yeersen,Chen, Qian-Qian,Fu, Shun-Guo,Chang, Shuai-Jun,Zhang, Xu-Xu,Zhang, Zhi-Liang,Wang, Xiao
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supporting information
p. 1280 - 1285
(2021/02/26)
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- Development of disulfide-derived fructose-1,6-bisphosphatase (FBPase) covalent inhibitors for the treatment of type 2 diabetes
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Fructose-1,6-bisphosphatase (FBPase), as a key rate-limiting enzyme in the gluconeogenesis (GNG) pathway, represents a practical therapeutic strategy for type 2 diabetes (T2D). Our previous work first identified cysteine residue 128 (C128) was an important allosteric site in the structure of FBPase, while pharmacologically targeting C128 attenuated the catalytic ability of FBPase. Herein, ten approved cysteine covalent drugs were selected for exploring FBPase inhibitory activities, and the alcohol deterrent disulfiram displayed superior inhibitory efficacy among those drugs. Based on the structure of lead compound disulfiram, 58 disulfide-derived compounds were designed and synthesized for investigating FBPase inhibitory activities. Optimal compound 3a exhibited significant FBPase inhibition and glucose-lowering efficacy in vitro and in vivo. Furthermore, 3a covalently modified the C128 site, and then regulated the N125–S124–S123 allosteric pathway of FBPase in mechanism. In summary, 3a has the potential to be a novel FBPase inhibitor for T2D therapy.
- Xu, Yi-xiang,Huang, Yun-yuan,Song, Rong-rong,Ren, Yan-liang,Chen, Xin,Zhang, Chao,Mao, Fei,Li, Xiao-kang,Zhu, Jin,Ni, Shuai-shuai,Wan, Jian,Li, Jian
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- Iodine mediated direct coupling of benzylic alcohols with dithiocarbamate anions: An easy access of S-benzyl dithiocarbamate esters under neat reaction condition
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An efficient, metal and solvent free synthesis of S-benzylic dithiocarbamate esters has been demonstrated via the iodine mediated direct C-S coupling of benzylic alcohols with dithiocarbamate anions generated in-situ by the reactions of amines and carbon disulphide. All the reactions were very fast (15–30 min) and performed under open air atmosphere. Cyclic and acyclic secondary amines, primary amine, aromatic amine actively participated in the one-pot coupling reactions with different benzylic alcohols. Non benzylic alcohols offer the synthesis of O-thiocarbamate compounds under the identical reaction condition.
- Dutta, Soumya,Saha, Amit
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- Disulfiram as a potent metallo-β-lactamase inhibitor with dual functional mechanisms
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We report a promising NDM-1 inhibitor, disulfiram, which can covalently bind to NDM-1 by forming an S-S bond with the Cys208 residue. Its copper-containing metabolite in vivo, Cu(DTC)2, also inactivated NDM-1 through oxidizing the Zn(ii) thiolate site of the enzyme, therefore exhibiting dual functional inhibitory potential against B1 and B2 subclass MβLs.
- Chen, Cheng,Li, Jia-Qi,Sun, Le-Yun,Wu, Lin-Yu,Yang, Ke-Wu
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supporting information
p. 2755 - 2758
(2020/03/17)
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- One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni's reagent
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A one-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates by the reaction of secondary amines, carbon disulfide and Togni's reagent is described. The reactions proceed in moderate to good yields. A similar reaction using a primary aliphatic amine afforded the corresponding isothiocyanate in high yield. A variable temperature NMR study revealed a rotational barrier of 14.6, 18.8, and 15.9 kcal/mol for the C-N bond in the dithiocarbamate moiety of piperidine, pyrrolidine, and diethylamine adducts, respectively. In addition, the calculated barriers of rotation are in reasonable agreement with the experiments.
- Halimehjani, Azim Ziyaei,Dra?ínsky, Martin,Beier, Petr
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supporting information
p. 2502 - 2508
(2017/12/06)
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- Pyruvate dehydrogenase kinase inhibitor and application thereof
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The invention provides a pyruvate dehydrogenase kinase inhibitor and an application thereof, specifically a compound as shown in a formula I described in the specification or pharmaceutically acceptable salts thereof. The compound has excellent effects of inhibiting pyruvate dehydrogenase kinase activity and resisting tumors. The invention also provides a pharmaceutical composition containing the compound provided by the invention and the application thereof in the aspect of inhibiting pyruvate dehydrogenase kinase.
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Paragraph 0107; 0108; 0109; 0110; 0119; 0120; 0121
(2017/08/28)
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- Role of disulfide linkage in action of bis(dialkylaminethiocarbonyl)disulfides as potent double-Edged microbicidal spermicide: Design, synthesis and biology
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Trichomoniasis and candidiasis are amongst the most common morbidity-causing reproductive tract infections, generally treated by Metronidazole and Fluconazole respectively. Poor vaginal efficacy, drug-resistance and non-spermicidal nature limit their use as topical microbicidal contraceptives. Bis(dialkylaminethiocarbonyl)disulfides (4-38) were designed as dually active, non-surfactant molecules capable of eliminating Trichomonas vaginalis and Candida strains as well as irreversibly immobilizing 100% human sperm instantly, at doses non-cytotoxic to human cervical epithelial cells and vaginal microflora in vitro. Compounds 12, 16, 17 were fifty times more active than nonoxynol-9, OTC vaginal spermicide, and compounds 12 and 17 have shown remarkable in vivo activity in rabbit model. Most promising compound 17 has shown promise for further development as a double-edged vaginal microbicide due to their improved activity and safety along with notable in vivo trichomonicidal activity. Role of disulfide group was established by loss of spermicidal activity on chemical modifications (39-56). These disulfides might be targeting thiol groups present over cell membrane of human sperm and Trichomonas as shown by fluorescence labeling of free thiols.
- Lal, Nand,Jangir, Santosh,Bala, Veenu,Mandalapu, Dhanaraju,Sarswat, Amit,Kumar, Lalit,Jain, Ashish,Kumar, Lokesh,Kushwaha, Bhavana,Pandey, Atindra K.,Krishna, Shagun,Rawat, Tara,Shukla, Praveen K.,Maikhuri, Jagdamba P.,Siddiqi, Mohammad I.,Gupta, Gopal,Sharma, Vishnu L.
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p. 275 - 290
(2016/04/26)
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- Reduced graphene oxide as recyclable catalyst for synthesis of Bis(aminothiocarbonyl)disulfides from secondary amines and carbon disulfide
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The reaction of secondary amines with CS2 under mild conditions using reduced graphene oxide (rGO) as a green catalyst was reported, which provided an efficient access to the one-pot synthesis of bis(aminothiocarbonyl) disulfides. The rGO can be recycled at least four times without any loss of catalytic activity. A plausible mechanism was proposed.
- Wang, Meishuang,Song, Xianghai,Ma, Ning
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p. 1233 - 1239
(2014/07/21)
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- Cerium ammonium nitrate-catalyzed aerobic oxidative coupling of dithiocarbamates: Facile synthesis of thioureas and bis(aminothiocarbonyl)disulfides
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Diverse disubstituted and trisubstituted thioureas were synthesized by the condensation of dithiocarbamate TEA (or DABCO) salts and amines using cerium ammonium nitrate (CAN) as a catalyst in high yields at room temperature. It is a one-pot method and it is unnecessary to isolate isothiocyanates. This reaction probably took place through nucleophilic addition of amines to isothiocyanates, which were generated by oxidative coupling of dithiocarbamates and the following decomposition of bis(aminothiocarbonyl)disulfides. When secondary amines and CS2served as the reactants, bis(aminothiocarbonyl)disulfides were obtained via tandem nucleophilic addition/oxidative coupling reactions in moderate to excellent yields. In all the coupling reactions, the oxidant was air and CAN possibly acted as an SET catalyst.
- Li, Tian-Tian,Song, Xiang-Hai,Wang, Mei-Shuang,Ma, Ning
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p. 40054 - 40060
(2014/12/10)
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- Development of an improved method for conversion of thiuram disulfides into N,N-dialkylcarbamoyl halides and derivatives
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A convenient procedure for preparing N,N-disubstituted carbamoyl halides is reported. It consists of two steps: (1) reaction of carbon disulfide and a secondary amine in the presence of a polar organic solvent and oxygen to produce the corresponding tetraalkyl thiuram disulfides and (2) reaction of tetraalkyl thiuram disulfide with a halide in the presence of an aprotic organic solvent to produce the corresponding N,N-disubstituted carbamoyl halide. Copyright Taylor & Francis Group, LLC.
- Adeppa,Rupainwar,Misra, Krishna
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experimental part
p. 285 - 290
(2011/03/20)
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- Exploring the structural requirements for inhibition of the ubiquitin E3 ligase breast cancer associated protein 2 (BCA2) as a treatment for breast cancer
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The zinc-ejecting aldehyde dehydrogenase (ALDH) inhibitory drug disulfiram (DSF) was found to be a breast cancer-associated protein 2 (BCA2) inhibitor with potent antitumor activity. We herein describe our work in the synthesis and evaluation of new series of zinc-affinic molecules to explore the structural requirements for selective BCA2-inhibitory antitumor activity. An N(C - S)S - S motif was found to be required, based on selective activity in BCA2-expressing breast cancer cell lines and against recombinant BCA2 protein. Notably, the DSF analogs (3a and 3c) and dithio(peroxo)thioate compounds (5d and 5f) were found to have potent activity (submicromolar IC50) in BCA2 positive MCF-7 and T47D cells but were inactive (IC50 > 10 μM) in BCA2 negative MDA-MB-231 breast cancer cells and the normal breast epithelial cell line MCF10A. Testing in the isogenic BCA2 +ve MDA-MB-231/ER cell line restored antitumor activity for compounds that were inactive in the BCA2 -ve MDA-MB-231 cell line. In contrast, structurally related dithiocarbamates and benzisothiazolones (lacking the disulfide bond) were all inactive. Compounds 5d and 5f were additionally found to lack ALDH-inhibitory activity, suggestive of selective E3 ligase-inhibitory activity and worthy of further development.
- Brahemi, Ghali,Kona, Fathima R.,Fiasella, Annalisa,Buac, Daniela,Soukupová, Jitka,Brancale, Andrea,Burger, Angelika M.,Westwell, Andrew D.
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experimental part
p. 2757 - 2765
(2010/08/20)
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- Bis(dialkylaminethiocarbonyl)disulfides as potent and selective monoglyceride lipase inhibitors
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Monoglyceride lipase (MGL) inhibition may offer an approach in treating diseases in which higher 2-arachidonoyglycerol activity would be beneficial. We report here the synthesis and pharmacological evaluation of bis(dialkylaminethiocarbonyl)disulfide derivatives as irreversible MGL inhibitors. Inhibition occurs through interactions with MGL C208 and C242 residues, and these derivatives exhibit high inhibition selectivity over fatty acid amide hydrolase, another endocannabinoid-hydrolyzing enzyme. 2009 American Chemical Society.
- Kapanda, Coco N.,Muccioli, Giulio G.,Labar, Geoffray,Poupaert, Jacques H.,Lambert, Didier M.
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experimental part
p. 7310 - 7314
(2010/07/14)
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- Carbon tetrabromide promoted reaction of amines with carbon disulfide: Facile and efficient synthesis of thioureas and thiuram disulfides
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A novel carbon tetrabromide promoted one-pot reaction of amines and carbon disulfide under mild conditions has been developed, which provides a straightforward and efficient access to thioureas and thiuram disufides, depending on the nature of the amines employed. The promotion effect is explained as the transient formation of a sulfenyl bromide intermediate from dithiocarbamate and carbon tetrabromide during the reaction. Georg Thieme Verlag Stuttgart · New York.
- Liang, Fushun,Tan, Jing,Piao, Chengri,Liu, Qun
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experimental part
p. 3579 - 3584
(2009/07/04)
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- Combinations for the treatment of fungal infections
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The invention features methods and compositions for treating a patient diagnosed with, or at risk for developing, a fungal infection.
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- Thiocarbamoylation of amine-containing compounds 5. The mechanism of reactions of tetramethylthiuram disulfide with aliphatic amines
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Thiocarbamoylation of aliphatic amines with tetramethylthiuram disulfide (TMTD) was studied. The reactions were established to proceed according to a two-stage mechanism. In the first stage, S-(thiocarbamoyl)thiohydroxylamines and dimethyl dithiocarbamates are formed. The latter exist in equilibrium with dimethyldithiocarbamic acid, which can undergo decomposition to give dimethylamine and carbon disulfide. In the second stage, several competitive transformations of these intermediates into the final products occur, viz., (1) the reactions of CS2 with primary amines on heating (70-110 deg C) yield mixed and symmetrical thioureas and the reactions of CS2 with secondary amines give symmetrical dithiocarbamates, and (2) insertion of CS2 into S-(thiocarbamoyl)thiohydroxylamines affords thiuram disulfides. Thiuram disulfides formed from primary amines decompose to give isothiocyanates, which are converted into thioureas by condensation with amines, whereas thiuram disulfides which are obtained in the reactions with secondary amines and which cannot form thioureas react with amines analogously to TMTD.
- Boi, Luu Van
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p. 335 - 343
(2007/10/03)
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- Sodium chlorite - Yet another oxidant for thiols to disulphides
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An efficicient oxidative coupling of thiols to disulphides is described using sodium chlorite which has good synthetic and commercial relevance.
- Ramadas,Srinivasan
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p. 227 - 234
(2007/10/02)
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- ZUR UMSETZUNG VON ARYLMETHYLKETONEN MIT SCHWEFEL, SEKUNDAEREN AMINEN UND SCHWEFELDIOXID
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The acetophenones 2 react with different sulfurdioxide-secondary amine adducts 1 and sulfur to yield the red-coloured zwitterionic 2-imino-dithioacetates 3.Enamines can be proved to be intermediates in this reaction.Thus enamines 5 and other derivatives such as acetophenone anil, acetophenone diethyl acetal and diphenacyl sulfide also give 3.In the absence of 1, 3a react with hydrogen sulfide to form the thioamide of phenylacetic acid 8. Key words: 2-Iminio-dithioacetates; iminium salts; zwitterionic; SO2-secondary amin adducts; Willgerodt-Kindler-reaction; enamines; heptathiocanes.
- Matschiner, Hermann,Maschmeier, Claus-Peter,Maier, Nadja,Hansen, Jens
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p. 223 - 230
(2007/10/02)
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- Synthesis, characterization and evaluation of biological activity of palladium (II) and platinum (II) complexes with dithiocarbamic acids and their derivatives as ligands
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We report the preparation and characterization of new complexes of palladium (II) and platinum (II) with some heterocyclic containing dithiocarbamate ligands, such as piperidine-, morpholine-, and thiomorpholine-dithiocarbamate, their methyl esters and the corresponding thiouramdisulphides. These compounds have been studied through spectroscopic techniques, IR spectra, and electronic spectra, thermogravimetric and conductivity measurements. Thermal decomposition of the complexes takes place through a multi-step process involving pyrolysis of the organic moiety that leads to palladium oxide and platinum sponge respectively. All the complexes have been tested for cytostatic activity on KB cells and the most effective compounds also against L1210 and P388 cells.
- Marcheselli,Preti,Tagliazucchi,Cherchi,Sindellari,Furlani,Papaioannou,Scarcia
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p. 347 - 352
(2007/10/02)
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- OXIDATION OF DERIVATIVES OF DITHIOCARBAMIC ACID WITH NITROUS ACID
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The oxidation of derivatives of dithiocarbamic acid with nitrous acid was studied.Analysis of the kinetic relations showed that the rate-determining step of the reaction is the formation of the nitrosyl cation.
- Shavetov, V. A.,Zolotov, A. N.,Mokrushin, V. S.
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p. 739 - 742
(2007/10/02)
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- Reduction Potentials of Thiuram Disulfide/Dithiocarbamate Couples in Acetone/Water
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Reduction potentials relative to the saturated calomel electrode, Eo, of a series of thiuram disulfide/dithiocarbamate couples have been measured in 30percent v/v water in acetone and at μ 0.2 mol l-1 (NaNO3) by a combination of potentiometric measurements and equilibrium constant determinations for thiolate/disulfide interchange reactions.Eo values lie in the range -250 to -340 mV which place dithiocarbamates as intermediate between thiophenolate (Eo -540 mV) and ethylxanthate (Eo -206 mV) in reducing properties.The significant effect on Eo of varying the substituents on the nitrogen in the dithiocarbamates correlates with the substituent effects on the acid dissociation constants of the parent dithiocarbamic acid and with trends in the half-wave potentials for metal-based oxidation and reduction of transition metal dithiocarbamate complexes.
- Nichols, Peter J.,Grant, Michael W.
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p. 2455 - 2463
(2007/10/02)
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- Pesticidal compositions containing phosphoric esters and divalent sulphur compounds
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Pesticidal composition comprising: a pesticidal, phosphoric ester the molecule of which has at least one alkyl group of 1 to 3 carbon atoms, 0.05 to 10% of an agent stabilizing the said ester against decomposition by protonisation, together with adjuvants characterized in that the stabilizing agent comprises at least one sulphur compound containing per molecule at least one divalent sulphur atom of which one valence is bonded to an atom chosen from sulphur, carbon, nitrogen, hydrogen, and metals capable of giving a salt, the other valence being bonded to an atom chosen from hydrogen, the carbon atom already noted, a second carbon atom, the nitrogen atom already noted, a second nitrogen atom, the metal atom already noted in the case of a metal of valence greater than one, a second atom of metal and oxygen when the first valence is not attached to an atom of hydrogen, the proportion of sulphur calculated with reference to the weight of the sulphur compound being between 5 and 99%. Process for stabilizing a phosphoric ester of which the molecule possesses at least one alkyl group containing 1 to 3 carbon atoms characterized in that there is added to the phosphoric ester or to a mixture which contains it, 0.05 to 10% calculated on the weight of the phosphoric acid ester of an agent capable of stabilizing the said phosphoric ester against protonisation and comprising at least one sulphur compound such as that defined thereupon.
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