- Method for synthesizing 1, 2, 4-triazole-3-carboxylic acid methyl ester
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The invention discloses a method for synthesizing 1, 2, 4-triazole-3-carboxylic acid methyl ester, and belongs to the field of organic chemistry. The method comprises the following reaction steps: reacting trichloroacetonitrile 1 with formylhydrazine 2 to generate an intermediate 3, then carrying out cyclization reaction to obtain an intermediate 4, and finally carrying out alcoholysis reaction togenerate 1, 2, 4-triazole-3-carboxylic acid methyl ester 5. According to the method, only three steps of reaction are needed, the overall yield is high, dangerous diazotization deamination reaction in a traditional synthesis process is avoided, the safety risk in the reaction process is reduced, and meanwhile the production cost can be reduced.
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Paragraph 0026-0027; 0030-0032; 0035-0037; 0040-0042; 0045
(2020/11/01)
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- Synthesis process of ribavirin intermediate and the intermediate
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The invention discloses a synthesis process of a ribavirin intermediate and the intermediate. 2-hydrazinyl-2-oxoacetate is used as a raw material, and the ribavirin intermediate 1,2,4-triazole-3-formamide is obtained by condensation with orthoformate triester, ammonolysis and cyclization in sequence. According to the process, the 2-hydrazinyl-2-oxoacetate is adopted as the initial raw material, the raw material is easily available and cheap, the synthesis route is short, expensive raw materials such as hypophosphorous acid are not adopted, dangerous raw materials such as hydrogen peroxide arenot used, a diazotization reaction which is a dangerous process is not adopted, reaction condition is mild, the whole process is almost free of generation of wastewater and solid waste; and the process is green, simple to operate and high in yield.
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Paragraph 0094-0096
(2020/08/12)
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- Structure Kinetics Relationships and Molecular Dynamics Show Crucial Role for Heterocycle Leaving Group in Irreversible Diacylglycerol Lipase Inhibitors
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Drug discovery programs of covalent irreversible, mechanism-based enzyme inhibitors often focus on optimization of potency as determined by IC50-values in biochemical assays. These assays do not allow the characterization of the binding activity (Ki) and reactivity (kinact) as individual kinetic parameters of the covalent inhibitors. Here, we report the development of a kinetic substrate assay to study the influence of the acidity (pKa) of heterocyclic leaving group of triazole urea derivatives as diacylglycerol lipase (DAGL)-α inhibitors. Surprisingly, we found that the reactivity of the inhibitors did not correlate with the pKa of the leaving group, whereas the position of the nitrogen atoms in the heterocyclic core determined to a large extent the binding activity of the inhibitor. This finding was confirmed and clarified by molecular dynamics simulations on the covalently bound Michaelis-Menten complex. A deeper understanding of the binding properties of covalent serine hydrolase inhibitors is expected to aid in the discovery and development of more selective covalent inhibitors.
- Janssen, Antonius P.A.,Van Hengst, Jacob M.A.,Béquignon, Olivier J.M.,Deng, Hui,Van Westen, Gerard J.P.,Van Der Stelt, Mario
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p. 7910 - 7922
(2019/10/11)
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- Preparation method for triazole derivative
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The invention discloses a preparation method for a triazole derivative represented by a formula (1) shown in the description. The method comprises the following steps: under protection of an inert gas, mixing a compound represented by a formula (2) shown in the description, an acidic substance, a reducing agent and a solvent, adding a sodium nitrite aqueous solution at temperature of -40 to 20 DEGC, performing a reaction at temperature of -20 to 50 DEG C for 0.5-5 h, performing filtration, washing the filter cake, and performing drying to obtain the triazole derivative represented by the formula (1). The method disclosed by the invention avoids separation of dangerous intermediate compounds; and meanwhile, a two step reaction of diazotization and reduction is completed in one pot, so thatthe production risk and costs of the triazole derivative are significantly reduced.
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Paragraph 0022-0026; 0027; 0028; 0029-0054; 0055-0072
(2018/11/27)
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- Chemoenzymatic method of 1,2,4-triazole nucleoside synthesis: Possibilities and limitations
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Possibilities and limitations of chemoenzymatic synthesis of novel structural analogues of an antiviral preparation of Ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) were established. A synthesis of various amides of 1H-1,2,4-triazole-3-carboxylic acid and its 5-substituted analogues - potential substrates of purine nucleoside phosphorylase - has been described. Comparative efficiency of preparation methods of these amides, as well as the methods of introduction of functional groups to the C5 position of heterocyclic system, were investigated. Novel analogues of Ribavirin containing various substitutes in the carboxamide group were synthesized. A biotechnological method was developed for the preparation of 1-β-D-ribofuranozyl-1,2,4-triazole-3-carbonitryl, an intermediate in the synthesis of Viramidine, the modern analogue of Ribavirin.
- Konstantinova,Chudinov,Fateev,Matveev,Zhurilo,Shvets,Miroshnikov
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- ENZYMATIC PREPARATIONS AND REGIOCHEMICAL PROPERTIES OF SOME NEW ADP-RIBOSYLATED 1,2,4-TRIAZOLES
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NAD nucleosidase-catalysed trans-ADP-ribosylation has been investigated for some 1,2,4-triazole bases.The unsubstituted base 1 provided N4-ribosylated triazoles (14 and 9), whereas 3-substituted (amino, chloro, mercapto, and carbamoyl)triazoles 2-4 and 6 underwent a regiospecific N1-ribosylation to produce the corresponding triazole adenine dinucleotides 10-13 in a good or moderate yield.Dinucleotide structures and the site of ribosylation were verified by 1H and 15N NMR spectrometries.The 3-carbamoyltriazole dinucleotide 13 can be a useful intermediate on the road to the antiviral agent, ribavirin, 18.
- Tono-oka, Shuichi,Azuma, Ichiro
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p. 297 - 300
(2007/10/02)
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