29984-33-6

Usage

Uses

Used in Antiviral Applications:
Vidarabine monophosphate is used as an antiviral agent for disrupting viral DNA synthesis. It acts as a competitive viral DNA polymerase inhibitor, making it active against herpes simplex and varicella zoster viruses in vivo.
Used in Chronic Hepatitis B Treatment:
Vidarabine monophosphate is used as a therapeutic agent for treating chronic hepatitis B, demonstrating quick effects and clear curative effects in patients.
Used in Herpes Infections Treatment:
Vidarabine monophosphate is used as an antiviral agent for treating various herpes infections, including herpes zoster, herpes simplex, and genital herpes, due to its broad-spectrum anti-virus effect and ability to inhibit a variety of DNA viruses.
Used in Clinical Anti-Virus Treatment:
Vidarabine monophosphate is used as a common drug in clinical settings for anti-virus treatment, particularly for the aforementioned viral infections.

Safety Profile

Moderately toxic byintraperitoneal route. When heated to decomposition itemits very toxic fumes of POx and NOx.

InChI:InChI=1/C10H14N5O7P/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(22-10)1-21-23(18,19)20/h2-4,6-7,10,16-17H,1H2,(H2,11,12,13)(H2,18,19,20)/p-2/t4-,6-,7+,10-/m1/s1

Upstream product

• 78-40-0 triethyl phosphate 
• 5536-17-4 arabinosyl adenine 
• 52940-98-4 6-acetylamino-9-[O³-acetyl-O⁵-phosphono-O²-(toluene-4-sulfonyl)-β-D-ribofuranosyl]-7,9-dihydro-purin-8-one 
• 61-19-8 5'-adenosine monophosphate 
• 28220-12-4 O^2'-(toluene-4-sulfonyl)-[5']adenylic acid 
• 28220-13-5 8-bromo-O^2'-(toluene-4-sulfonyl)-[5']adenylic acid 
• 52989-04-5 phosphoric acid mono-((6aS)-7c-acetoxy-4-acetylamino-(6ar,9ac)-6a,7,8,9a-tetrahydro-furo[2',3':4,5]oxazolo[3,2-e]purin-8t-ylmethyl) ester 
• 58-61-7 L-adenosine 

Relevant academic research and scientific papers

Synthesis method and application of vidarabine monophosphate

The invention belongs to the field of medicine synthesis, and discloses a synthesis method and application of vidarabine monophosphate. According to the synthesis method, 5-iodo-2-((phosphonooxy) methyl)-4-(tosyloxy)tetrahydrofuran-3-yl acetate and tert-butyl (8-hydroxy-9H-purin-6-yl)carbamate are subjected to condensation, epoxidation, ring opening and desulfurization reaction, and the vidarabine monophosphate is synthesized. According to the synthesis method of vidarabine monophosphate, provided by the invention, the industrial production steps are further simplified, the total reaction yield is improved, and the industrial production cost is reduced. The method is suitable for synthesizing vidarabine monophosphate, and the synthesized vidarabine monophosphate is used for preparing vidarabine monophosphate for injection.

Production process of vidarabine monophosphate

The invention belongs to the technical field of preparation of vidarabine monophosphate and particularly relates to a production process of vidarabine monophosphate. The production process of vidarabine monophosphate comprises the following steps of S1 dissolving vidarabine into organic solvent and cooling down the mixture; S2, adding in phosphoryl chloride to perform thermal reaction until that the residual content of the vidarabine is not higher than 3% of the added amount; S3, adding in palladium catalysts for catalytic reduction, then filtering reaction products, removing the solvent fromthe obtained filter liquor to obtain crude vidarabine monophosphate; S4, recrystallizing the crude vidarabine monophosphate obtained in S3 for purification. The production process of vidarabine monophosphate introduces the phosphoryl chloride relatively low in reactivity to react with the raw vidarabine, the reaction process is mild and easy to control, so that the produced quantity of side products can be reduced from the source; meanwhile, the novel palladium catalysts can selectively reduce introduced ether groups, thereby simplifying purification processes and achieving high product yieldand purity.

Preparation method of vidarabine monophasphate

The invention discloses a preparation method of vidarabine monophosphate. The preparation method comprises the following two steps: crude product synthesis and crude product refining. In a crude product synthesis stage, reaction conditions are controlled severely, side reaction and production of related substances are reduced effectively, and high percent conversion of a target product is ensured.Meanwhile, because most of side products of reaction are dissolved in the reaction system and the target product is not dissolved in the reaction system basically, aftertreatment is facilitated to improve the purity of the product. The method is simple in process, high in product yield, high in purity and high in reaction selectivity; any special equipment is not used during production; and the preparation method is suitable for industrial production.

Preparation method of vidarabine monophosphate

The invention provides a preparation method of vidarabine monophosphate. According to the method, vidarabine and phosphoric acid are used as raw materials; highly acidic ion exchange resin is used as a catalyst; the vidarabine monophosphate is generated through a one-step esterification reaction. The process route is short; the yield is higher; the resin serving as the catalyst can be repeatedly used after being regenerated. The use of phosphorus oxychloride which is high in smoke formation and high in pungency is avoided in the reaction; the production operational safety is improved; the preparation method is more environment-friendly. The method is simple to operate; the industrialized production is easily realized; the production efficiency is improved.

Synthetic method of vidarabine monophosphate

The invention provides a synthetic method of vidarabine monophosphate. The synthetic method comprises the following steps: a) making an intermediate shown as a formula (II) react with a solid sulfurizing agent and strong-acid ion exchange resin to obtain an intermediate shown as a formula (III), wherein the solid sulfurizing agent is selected from sodium sulfide, a sodium sulfide hydrate, sodium hydrosulfide or a sodium hydrosulfide hydrate; b), desulfurizing the intermediate shown as the formula (III) to obtain the vidarabine monophosphate. In the method, the intermediate shown as the formula (II) is subjected to sulfhydrylation through the solid sulfurizing agent such as the sodium sulfide, the sodium bisulfide, the sodium sulfide hydrate or the sodium hydrosulfide hydrate and the strong-acid ion exchange resin, and is desulfurized to obtain the vidarabine monophosphate, so that the use of hydrogen sulfide is avoided, and the pressure on the environment is lowered. Meanwhile, by adopting the synthetic method provided by the invention, the yield is 30 percent or more, and the purity of an obtained product is 99.8 percent or more.

Synthesis technology of vidarabine monophosphate

The invention discloses a synthesis technology of vidarabine monophosphate. The synthesis technology comprises the following steps: suspension dissolving vidarabine into an aprotic polar solvent firstly, carrying out reaction on a reactant and pyrophosphoryl chloride at low temperature, then carrying out hydrolysis quenching, regulating a pH value to 2.5-3, and precipitating the vidarabine monophosphate, wherein the purity of a crude product is 95 percent or above; and finally, carrying out recrystallization treatment on the vidarabine monophosphate to improve the purity of the vidarabine monophosphate to 99 percent or above with the maximum single impurity content controlled to be 0.2 percent or below. The synthesis technology of the invention has the advantages of high yield and less impurities and is suitable for industrial production.

High-purity vidarabine monophosphate preparation method

The invention provides a vidarabine monophosphate preparation method. The method comprises the following steps: 1) mixing adenine arabinoside in phosphate alkane este, adding a phosphorylation reagent, performing a temperature control reaction; 2) slowly adding a reacted reaction solution in purified water, performing hydrolysis; 3) adding an organic solvent for extraction, adjusting sodium hydroxide for adjusting the pH value of a water layer to 6.0-8.0 to obtain an upper column stock solution; 4) after the upper column stock solution is diluted, performing exchange adsorption by a highly basic-type anion exchange resin at certain flow velocity; 5) eluting the material by an eluate with proper concentration, collecting the eluate with an OD value being greater than or equal to 100; and 6) concentrating the eluate, crystallizing the material and filtering the material to obtain vidarabine monophosphate. The highly basic-type anion exchange resin is selected from 201*7 and 201*8 highly basic-type anion exchange resin; and the eluate in the step 5) is selected from 0.01-0.05 mol/L of a hydrochloric acid aqueous solution and a sodium chloride aqueous solution with concentration of 0.3-0.8%. The preparation method has the advantages of high purity, high yield, and easy and convenient operation.

A phosphorylated process method of arabinose phosphate adenosine

The invention provides a phosphorylation method for preparing vidarabine monophosphate. The method is specifically as below: using vidarabine as a starting material; conducting phosphorylation on the material under the protection of inert gas and under the effect of catalyst; and conducting active carbon decoloration treatment to obtain a vidarabine monophosphate crude product. The process route is simple, low-cost and high-yield; and compared with the prior art, the production process has significantly reduced toxicity, and is suitable for process production.

Immobilized Drosophila melanogaster deoxyribonucleoside kinase (DmdNK) as a high performing biocatalyst for the synthesis of purine arabinonucleotides

Fruit fly (Drosophila melanogaster) deoxyribonucleoside kinase (DmdNK; EC: 2.7.1.145) was characterized for its substrate specificity towards natural and non-natural nucleosides, confirming its potential in the enzymatic synthesis of modified nucleotides. DmdNK was adsorbed on a solid ion exchange support (bearing primary amino groups) achieving an expressed activity >98%. Upon cross-linking with aldehyde dextran, expressed activity was 30-40%. Both biocatalysts (adsorbed or cross-linked) were stable at pH 10 and room temperature for 24 h (about 70% of retained activity). The cross-linked DmdNK preparation was used for the preparative synthesis of arabinosyladenine monophosphate (araA-MP) and fludarabine monophosphate (FaraAMP). Upon optimization of the reaction conditions (50 mM ammonium acetate, substrate/ATP ratio= 1:1.25, 2 mM MgCl2, 378C, pH 8) immobilized DmdNK afforded the title nucleotides with high conversion (>90%), whereas with the soluble enzyme lower conversions were achieved (78-87%). Arabinosyladenine monophosphate was isolated in 95% yield and high purity (96.5%).

A nucleotide dimer synthesis without protecting groups using montmorillonite as catalyst

A synthesis has been developed providing nucleotide dimers comprising natural or unnatural nucleoside residues. A ribonucleoside 5-phosphorimidazolide is added to a nucleoside adsorbed on montmorillonite at neutral pH with the absence of protecting groups. Approximately 30% of the imidazolide is converted into each 2-5 dimer and 3-5 dimer with the rest hydrolyzed to the 5-monophosphate. Experiments with many combinations have suggested the limits to which this method may be applied, including heterochiral and chimeric syntheses. This greener chemistry has enabled the synthesis of dimers from activated nucleotides themselves, activated nucleotides with nucleosides, and activated nucleotides with nucleotide 5-monophosphates.