- Carbonic anhydrase inhibitors: Synthesis of N-morpholylthiocarbonylsulfenylamino aromatic/heterocyclic sulfonamides and their interaction with isozymes I, II and IV
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Several aromatic/heterocyclic sulfonamides possessing free amino, imino or hydrazino moieties were transformed into the corresponding N-morpholylthiocarbonylsulfenyl derivatives, by reaction with N-morpholyldithiocarbamate in the presence of oxidizing age
- Scozzafava, Andrea,Supuran, Claudiu T.
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- 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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- 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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- 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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- Thiuram disulfide compound and synthesis process thereof
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The invention belongs to the field of rubber additives and particularly relates to a thiuram disulfide compound and a synthesis process thereof. The synthesis process comprises the following steps: (1) mixing secondary amine with alkaline liquid, then dropwise adding carbon disulfide, wherein the molar ratio of the secondary amine to the alkaline liquid to the carbon disulfide is 1 to (1-2) to (1-2), and reacting at the temperature of 30-60 DEG C to obtain a sodium dithioformate intermediate; (2) mixing and stirring the sodium dithioformate intermediate obtained in the step (1), dimethylsulfoxide and a dispersant, dropwise adding a strong acid catalyst and reacting at the temperature of 30-80 DEG C, wherein the molar ratio of the sodium dithioformate intermediate to the dimethylsulfoxide to the strong acid catalyst is 2 to (1-1.8) to (2-4), and the molar amount of the catalyst is metered by hydrogen ions; and generating a target product. The product yield of the reaction can reach 95%or above; through HPLC test of the product, the purity can reach up to 96%.
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Paragraph 0039-0043
(2019/03/25)
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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; 0122; 0123; 0124; 0125
(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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- 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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- A short, novel, and cheaper procedure for oligonucleotide synthesis using automated solid phase synthesizer
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Dimethylthiuram disulfide (DTD) has been developed as an efficient thiolation reagent during automated synthesis of oligonucleotides using phosphoramidite chemistry. Simultaneous thiolation and capping was accomplished by mixing DTD with capping solution B, which saved 20% of solvent consumption and compressed the four-step synthesis cycle to three. Large-scale (1 mmol) synthesis of phosphorothioate oligonucleotides has been demonstrated with excellent yield and purity.
- Song, Quanlai,Wang, Zhiwei,Sanghvi, Yogesh S.
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p. 629 - 633
(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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- 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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- REACTION OF BIS(MORPHOLINOTHIOCARBONYL)DISULPHIDE WITH IODINE. EXISTENCE OF A 1:1 CHARGE-TRANSFER PRECURSORY ADDUCT IN AN OXIDATION REACTION. ISOLATION AND CRYSTAL STRUCTURE OF BIS HEXADECAIODIDE
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The reaction of bis(morpholinothiocarbonyl) disulphide, S22, with iodine in ratios ranging between 1:1 and 1:10 has been investigated in CH2Cl2 by spectrophotometric measurements.The immediate production of the known 1:1 charge-transfer complex between the reagents is observed.This species evolves according to a first-order rate law to give a brown compound which has been isolated from concentrated CH2Cl2 solutions of I2 + S22 mixtures.An X-ray crystal structure analysis of this compound indicated that the crystals are triclinic, Space group P-1, with a = 7.834(2), b = 7.959(2), c = 24.142(4) Angstroem, α = 86.80(1), β = 88.55(1), γ = 70.86(1) deg, and Z = 2.The structure consists of bis cations, 2+, and of discrete polyiodide anions I164-.
- Bigoli, Francesco,Pellinghelli, Maria Angela,Crisponi, Guido,Deplano, Paola,Trogu, Emanuele Filiberto
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p. 1349 - 1354
(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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- Biologically oriented organic sulfur chemistry. 15. Organic disulfides and related substances. 41. Inhibition of the fungal pathogen Histoplasma capsulatum by some organic disulfides
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In an extension of promising inhibitory results in vitro against Histoplasma capsulatum, correlated earlier using substituent constants developed by regression analysis with 77 disulfides, one symmetrical and 14 unsymmetrical disulfides were prepared (3-17). About half were active in vitro against H. capsulatum (and one against Candida albicans). Groups that seemed most to lead to promising inhibition among the unsymmetrical disulfides were o-HO2CC6H4, (CH2)SO2Na, Me2NCCS), p-ClC6H4, and perhaps p-CH3C6H4; the first two also might be used to increase solubility. Earlier inhibitory promise of the morpholino group did not materialize. None of the group 3-17 was significantly active in vivo. The unsymmetrical disulfides were prepared by reaction of thiols with sulfenyl chlorides or with acyclic or cyclic thiosulfonates. Two six-membered heterocyclic disulfides (5 and 6) were prepared by a novel cyclization, in which carbon disulfide reacted with an (N-alkylamino)ethyl Bunte salt, followed by ring closure; an explanation is suggested for formation of a thiazoline when the N-alkyl group is absent. One of the disulfides disproportionated with astonishing ease (31; 0.3-1 h at 25°C).
- Field,Grimaldi,Hanley,Holladay,Ravichandran,Schaad,Tate
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p. 996 - 1001
(2007/10/04)
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