Tenofovir disoproxil

Base Information

• Chemical Name: Tenofovir disoproxil
• CAS No.: 201341-05-1
• Molecular Formula: C₁₉H₃₀N₅O₁₀P
• Molecular Weight: 519.448
• European Community (EC) Number: 606-442-6
• UNII: F4YU4LON7I
• DSSTox Substance ID: DTXSID5052757
• Nikkaji Number: J898.676B
• Wikipedia: Tenofovir_disoproxil
• Wikidata: Q27132753
• NCI Thesaurus Code: C47747
• RXCUI: 322248
• Metabolomics Workbench ID: 62918
• ChEMBL ID: CHEMBL1538
• Mol file: 201341-05-1.mol

Synonyms:(R)-9-(2-phosphonylmethoxypropyl)adenine;9-(2-phosphonomethoxypropyl)adenine;9-(2-phosphonylmethoxypropyl)adenine;9-(2-phosphonylmethoxypropyl)adenine, (+-)-isomer;9-(2-Phosphonylmethoxypropyl)adenine, (R)-isomer - T357098;9-(2-phosphonylmethoxypropyl)adenine, (S)-isomer;9-PMPA (tenofovir);Disoproxil Fumarate, Tenofovir;Disoproxil, Tenofovir;Fumarate, Tenofovir Disoproxil;tenofovir;tenofovir disoproxil;tenofovir disoproxil fumarate;Viread

Chemical Property of Tenofovir disoproxil

Chemical Property:

• Vapor Pressure: 2.06E-16mmHg at 25°C
• Refractive Index: 1.578
• Boiling Point: 642.733 °C at 760 mmHg
• PKA: 4.20±0.10(Predicted)
• Flash Point: 342.513 °C
• PSA: 195.25000
• Density: 1.459 g/cm³
• LogP: 3.61680
• Storage Temp.: -20°C
• XLogP3: 1.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 14
• Rotatable Bond Count: 17
• Exact Mass: 519.17302917
• Heavy Atom Count: 35
• Complexity: 698

Purity/Quality:

99% ^*data from raw suppliers

SRY ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)OC(=O)OCOP(=O)(COC(C)CN1C=NC2=C(N=CN=C21)N)OCOC(=O)OC(C)C
• Isomeric SMILES: C[C@H](CN1C=NC2=C(N=CN=C21)N)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C
• Recent ClinicalTrials: A Study of JNJ-73763989, JNJ-56136379, Nucleos(t)Ide Analogs, and Pegylated Interferon Alpha-2a in Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection
• Recent EU Clinical Trials: A Platform Study Evaluating the Efficacy and Safety of Investigational Therapies in Participants with Chronic Hepatitis B Infection (PREVAIL)
• Recent NIPH Clinical Trials: A Study of JNJ-73763989, JNJ-56136379, Nucleos(t)ide Analogs, and Pegylated Interferon Alpha-2a in Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection
• Description: Tenofovir disoproxil belongs to a class of medications called antiretroviral known as a nucleotide reverse transcriptase inhibitor, which is commonly used to treat the infection caused by the human immunodeficiency virus (HIV) generally in combination with other antiviral agents. It can also be used for prevention of HIV/AIDS among those people who are at high risk before exposure, such as injection through sexual transmission or injection of drugs. It functions by blocking reverse transcriptase, an enzyme vital to viral duplication in people infected HIV. Besides, it is effective to treat chronic hepatitis B, in which it helps prevent the enzymes needed for the hepatitis B virus to reproduce from working properly. However, tenofovir disoproxil does not cure HIV/AIDS or hepatitis B. It helps lower the amount of HIV or hepatitis B virus in the body and slow down the progression of the disease. Tenofovir was patented in 1996 and approved for use in the United States in 2001. Tenofovir disoproxil is a prodrug in a manner similar to that of adefovir dipivoxil. In both cases, the phosphate esters are removed through the action of plasma esterase, leading in this case to tenofovir, which differs from adefovir by the presence of the indicated methyl group. Tenofovir disoproxil exhibits good bioavailability (25%), which is improved in the presence of food (35%). The drug is approved for the treatment of HIV infections in adult patients. Tenofovir diphosphate is an HIV RT inhibitor. The active form of tenofovir is the tenofovir diphosphate, which competes with dATP for incorporation into viral DNA, and when incorporated, tenofovir diphosphate results in premature termination of DNA growth and inhibition of DNA polymerase. Tenofovir disoproxil is indicated for treatment-experienced patients with HIV-1. The drug also appears to be effective in treatment-naive patients, but initial approval is for treatment-experienced patients. The drug is administered as one tablet taken once daily. It is recommended that the drug be combined with other RT inhibitors or HIV PIs, which results in additive or synergistic activity.
• Uses: Tenofovir Disoproxil is a therapeutic option for nucleos(t)ide analog (NA)-experienced chronic hepatitis B (CHB) patients infected with hepatitis B virus (HBV). Also, it is an intermediate used in the synthesis of Tenofovir Disoproxil Dimer (T018515), which is a Tenofovir Disoproxil impurity.
• 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.

Technology Process of Tenofovir disoproxil

There total 25 articles about Tenofovir disoproxil which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 92.0%

tenofovir disoproxil muconate → tenofovir disoproxil (201341-05-1)

Guidance literature:

With sodium hydrogencarbonate; In dichloromethane; water; at 0 - 10 ℃; for 0.333333h;

Reference yield: 91.5%

chloromethyl isopropyl carbonate (35180-01-9) + tenofovir (147127-20-6) → tenofovir disoproxil (201341-05-1)

Guidance literature:

With tetrabutylammomium bromide; triethylamine; In 1-methyl-pyrrolidin-2-one; at 50 ℃; Temperature;

Reference yield: 37.0%

hydroxymethyl isopropyl carbonate + 9-[(R)-2-[[(S)-[bis(phenoxy)phosphinyl]]methoxy]propyl]adenine (342631-41-8) → tenofovir disoproxil (201341-05-1)

Guidance literature:

With 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine; In 1,2-dichloro-ethane; at 20 ℃; for 16h;

upstream raw materials:

chloromethyl isopropyl carbonate

tenofovir

(R)-N₄-dimethylaminomethylideno-9-(2-phosphonomethoxypropyl)adenine bis(isopropyloxycarbonyloxymethyl) ester

adenine

Downstream raw materials:

tenofovir

tenofovir disoproxil hemifumarate

tenofovir disoproxil fumarate

tenofovir disoproxil hemifumarate

Refernces

• 1、 -. "Preparation method of nucleoside phosphate prodrug". Paragraph 0018-0019. . Retrieved 2022/01/12.
• 2、 -. "METHODS FOR IMPROVING PURITY OF TENOFOVIR DISOPROXIL FUMARATE, AND COMPOSITIONS THEREOF". Paragraph 0188; 0196; 0198; 0200; 0202; 0204; 0206. . Retrieved 2020/07/16.