- 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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- 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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- 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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- Synthesis process of N, N'-dialkyl-N, N'-diphenylthiuram disulfide
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The invention relates to a synthesis process of N, N '-dialkyl-N, N'-diphenylthiuram disulfide. The conversion rate of raw materials is improved, the product yield reaches 98% or above and the productpurity reaches 98.5% or above through the measures of using a preferred catalyst, adding initial raw materials at a time, controlling side reactions through low-temperature oxidation and the like. According to the process, inorganic salt byproducts are not generated, the feeding operation is simple and convenient, the reaction is efficient and thorough, and meanwhile, a high-purity product is obtained.
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Paragraph 0022-0023; 0028-0029; 0032-0043
(2020/05/30)
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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 0044-0048
(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; 0138; 0139; 0140; 0141
(2017/08/28)
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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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- 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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