201341-05-1

Basic information

• Product Name: Tenofovir disoproxil
• Synonyms: (R)-(((((1-(6-AMino-9H-purin-9-yl)propan-2-yl)oxy)Methyl)phosphoryl)bis(oxy))bis(Methylene) diisopropyl dicarbonate;(R)-(((((1-(6-Amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoryl)-bis(oxy))bis(methylene) diis;2,4,6,8-Tetraoxa-5-phosphanonanedioicacid, 5-[[(1R)-2-(6-aMino-9H-purin-9-yl)-1-Methylethoxy]Methyl]-,1,9-bis(1-Methylethyl) ester, 5-oxide;TenofivirDisoproxilFumarate;SRY;Testis-determining factor;Tenofovir disoproxil, >=98%;Tenofovir disoproxil aspartate
• CAS NO: 201341-05-1
• Molecular Formula: C19H30N5O10P
• Molecular Weight: 519.44
• EINECS: 111-111-1
• Mol File: 201341-05-1.mol

Chemical Properties

• Boiling Point: 642.733 °C at 760 mmHg
• Flash Point: 342.513 °C
• Appearance: /
• Density: 1.459 g/cm³
• Vapor Pressure: 2.06E-16mmHg at 25°C
• Refractive Index: 1.578
• Storage Temp.: -20°C
• PKA: 4.20±0.10(Predicted)
• CAS DataBase Reference: Tenofovir disoproxil(CAS DataBase Reference)
• NIST Chemistry Reference: Tenofovir disoproxil(201341-05-1)
• EPA Substance Registry System: Tenofovir disoproxil(201341-05-1)

Safety Data

• Hazardous Substances Data: 201341-05-1(Hazardous Substances Data)

Usage

Uses

Used in HIV Treatment:
Tenofovir disoproxil is used as an antiretroviral agent for the treatment of HIV infections in adult patients. It is typically administered in combination with other reverse transcriptase inhibitors or protease inhibitors to achieve synergistic activity and improve treatment outcomes.
Used in Hepatitis B Treatment:
Tenofovir disoproxil is also used for the treatment of chronic hepatitis B, where it helps inhibit the enzymes required for the hepatitis B virus to reproduce, thus preventing the virus from multiplying and slowing down the progression of the disease.
Used as an Intermediate in Synthesis:
Tenofovir disoproxil serves as an intermediate in the synthesis of Tenofovir Disoproxil Dimer (T018515), which is a Tenofovir Disoproxil impurity. This application is relevant in the pharmaceutical industry for the development and production of related compounds and drugs.
Used in Pre-Exposure Prophylaxis (PrEP):
Tenofovir disoproxil can be used for prevention of HIV/AIDS among individuals at high risk before exposure, such as through sexual transmission or injection drug use. It functions by reducing the chances of acquiring the HIV infection when used as part of a comprehensive prevention strategy.

References

https://en.wikipedia.org/wiki/Tenofovir_disoproxil http://bodyandhealth.canada.com/drug/getdrug/viread https://www.drugbank.ca/drugs/DB00300

Clinical Use

Nucleoside reverse transcriptase inhibitor: Treatment of HIV in combination with other antiretroviral drugs Treatment of hepatitis B in compensated liver disease

Drug interactions

Potentially hazardous interactions with other drugs Antivirals: avoid with adefovir and cidofovir; reduces concentration of atazanavir, also concentration of tenofovir possibly increased; increased didanosine concentration resulting in increased toxicity (e.g. pancreatitis and lactic acidosis) - avoid; concentration increased by lopinavir and telaprevir. Co-administration with other drugs that are actively secreted via the tubular anionic transporter. Orlistat: absorption possibly reduced by orlistat.

Metabolism

Tenofovir is excreted mainly in the urine by both active tubular secretion and glomerular filtration.

InChI:InChI=1/C19H30N5O10P/c1-12(2)33-18(25)28-9-31-35(27,32-10-29-19(26)34-13(3)4)11-30-14(5)6-24-8-23-15-16(20)21-7-22-17(15)24/h7-8,12-14H,6,9-11H2,1-5H3,(H2,20,21,22)/t14-/m1/s1

Upstream product

• 35180-01-9 chloromethyl isopropyl carbonate 
• 147127-20-6 tenofovir 
• 14047-28-0 (R)-9-(2-hydroxypropyl)adenine 
• 180587-75-1 (R)-diethyl (((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate 
• 66224-66-6 adenine 
• 14047-27-9 (S)-1-(6-amino-9H-purin-9-yl) propan-2-ol 
• 202138-50-9 tenofovir disoproxyl fumarate 
• 160616-04-6 bis(2-propyl) (R)-9-(2-phosphonomethoxypropyl)adenine 
• 1432630-26-6 tenofovir disoproxil fumarate 
• 15571-48-9 bis(isopropoxy) magnesium 
• 342631-41-8 9-[(R)-2-[[(S)-[bis(phenoxy)phosphinyl]]methoxy]propyl]adenine 
• 922494-97-1 (R)-N₄-dimethylaminomethylideno-9-(2-phosphonomethoxypropyl)adenine bis(isopropyloxycarbonyloxymethyl) ester 

Downstream Products

• 147127-20-6 tenofovir 
• 1432630-26-6 tenofovir disoproxil hemifumarate 
• 211364-69-1 Tenofovir mono-POC 
• 1244022-53-4 C₂₀H₃₂N₅O₁₁P 
• 1432630-26-6 tenofovir disoproxil fumarate 
• 211364-69-1 mono-isopropyloxycarbonylmethyl 9-((R)-2-(phosphonomethoxy)propyl)adenine 
• 1432630-26-6 tenofovir disoproxil fumarate 
• 1432630-26-6 tenofovir disoproxil hemifumarate 

Relevant articles and documents

Green synthesis improvement of tenofovir disoproxil

Polyethylene glycol, known as 'Green Chemical', is a catalyst for the synthesis of tenofovir disoproxil. Some technological parameters were discussed by adoptting via single-factor experiments. Through the catalytic reaction, not only tenofovir disoproxil yield was improved but also by-products was reduced obviously. The results showed that the optimal conditions were as follows: 0.6 equiv PEG-600, 4.0 equiv triethylamine, 6.0 equiv N-methyl-2-pyrrolidone and temperature at 50°C for 16 h with a yield of 65.12 %.

Preparation method of nucleoside phosphate prodrug

The invention belongs to the field of pharmaceutical chemicals, and relates to a preparation method of a nucleoside phosphate prodrug. A diphenol phosphate intermediate A and an alcohol compound B are subjected to a transesterification reaction to obtain the nucleoside phosphate prodrug. According to the method, rapid synthesis of different nucleoside prodrugs is achieved through exchange of the base-catalyzed nucleoside diphenyl phosphate intermediate and alcohol, synthesis of a target compound is achieved through one-step reaction, meanwhile, use of strong acid and high-toxicity chlorides is avoided, the safety of generation can be improved, the cost is reduced, and emission of three wastes is reduced.

METHODS FOR IMPROVING PURITY OF TENOFOVIR DISOPROXIL FUMARATE, AND COMPOSITIONS THEREOF

Methods for producing tenofovir disoproxil fumarate with improved purity are provided. In particular, methods for producing tenofovir disoproxil fumarate with reduced levels of chloromethyl isopropyl carbonate are described. Also described are compositions containing tenofovir disoproxil fumarate with improved purity, and an analysis method that can be used to determine the purity of such compositions with improved accuracy and sensitivity.

Synthesis process of antiviral drug

The invention discloses a synthesis process of an antiviral drug. The process comprises the following steps: reacting adenine (II) with (R)- propylene carbonate (III) to prepare a compound IV, carrying out alkylation reaction on the compound IV and a compound V to prepare a compound VI, and carrying out esterolysis reaction to prepare a compound VII; and carrying out esterification reaction on theprepared compound VII and chloromethyl isopropyl carbonate, and salifying with fumaric acid to prepare the final product tenofovir disoproxil fumarate (I). The synthetic route is simple, the reactionconditions are mild, the generation of impurities is reduced, the total yield and purity of the product are improved, and the method is suitable for industrial production.

Method for preparing tenofovir disoproxil

The invention discloses a method for preparing tenofovir disoproxil and relates to the field of preparation of tenofovir disoproxil. The method for preparing the tenofovir disoproxil specifically comprises the following steps: A) preparing (R)-9-(2-hydroxypropyl) adenine; B) preparing (R)-9-(2-phosphonic acid methoxy-propyl) adenine di(ethyl) ester; C) preparing tenofovir; D) preparing tenofovir disoproxil; and E) carrying out finished product detection and inspection. Compared with the prior art, the method has the beneficial effects that while the medicine effect of the tenofovir disoproxilis ensured, the reaction steps are simplified, the yield is increased, the conversion rates of intermediates (R)-9-(2-hydroxypropyl) adenine, (R)-9-(2-phosphonic acid methoxy-propyl) adenine di(ethyl)ester and tenofovir reach 75%, 63.2% and 74.3% respectively, and the total yield of the tenofovir disoproxil is as high as 62.4% finally.

A method for preparing for [...] (by machine translation)

The invention relates to a method for preparing for [...]. Specifically, the invention relates to an industrial production level of preparation for fuwei two pyrrole fufu ester of the method, the method can improve the reaction yield, reducing the impurity, is simple and easy to control, is conducive to industrial expansion of production. (by machine translation)

A [...] and its preparation method for

The invention relates to the technical field of medicinal chemical engineering and particularly relates to a tenofovir disoproxil crystal form and a preparation method thereof. The tenofovir disoproxil has characteristic peaks when a diffraction angle 2[theta] is 7.3 +/- 0.2 degrees, 12.9 +/- 0.2 degrees, 14.4 +/- 0.2 degrees, 17.9 +/- 0.2 degrees, 19.1 +/- 0.2 degrees, 20.8 +/- 0.2 degrees and 22.9 +/- 0.2 degrees.

Synthetic method for tenofovir disoproxil

The invention discloses a synthetic method for tenofovir disoproxil. The method comprises the following steps: adding raw material tenofovir (PMPA), a phase transfer catalyst tetrabutylammonium bromide, an acid-binding agent and an auxiliary agent into an organic solvent under the protection of a nitrogen gas at room temperature, performing stirring for a period of time, performing heating to a certain temperature, adding chloromethyl isopropyl carbonate (POC) dropwise, performing a reaction for a period of time, after the reaction is completed, performing precipitation by brine ice to obtaincrude tenofovir disoproxil, performing filtration, adding a solvent, performing pulping, and performing drying to obtain the finished tenofovir disoproxil. According to the process provided by the invention, the appropriate reaction auxiliary agent is selected to reduce generation of impurities, multiple refining is avoided, the product purity is improved, the product yield is high, and the methodis suitable for large-scale industrial production.

Preparation method and application of tenofovir monoester

The invention belongs to the field of medicines, and in particular relates to a preparation method and application of tenofovir monoester. The method comprises the following steps: preparing tenofovirand chloromethyl isopropyl carbonate; dissolving the tenofovir into an organic solvent, adding an organic alkali and a catalyst, adding the chloromethyl isopropyl carbonate, and performing a reactionto obtain a solid tenofovir disoproxil; and performing hydrolysis on the solid tenofovir disoproxil in an alkali aqueous solution to obtain the tenofovir monoester. The preparation method of the tenofovir monoester provided by the invention has easily-available raw materials, is simple and convenient to operate, and has low requirements on equipment, and important significance for effectively controlling quality of tenofovir disoproxil fumarate.

Preparation method of tenofovir disoproxil hemifumarate

The invention provides a preparation method of tenofovir disoproxil hemifumarate, particularly a preparation method of tenofovir disoproxil hemifumarate in a one-pot manner. Through adding a water-binding agent, generation of impurities in a synthesis process of tenofovir disoproxil is controlled, and therefore, the intermediate tenofovir disoproxil does not need to be completely separated from the reaction system, reaction treatment steps are saved, the loss of the process is reduced, the purity of the prepared tenofovir disoproxil hemifumarate is greater than 99.0%, and the impurity tenofovir monosoproxil is less than 0.1%; and the total molar yield is stabilized at 77%-85%.