Adefovir dipivoxil

Base Information

• Chemical Name: Adefovir dipivoxil
• CAS No.: 142340-99-6
• Molecular Formula: C20H32N5O8P
• Molecular Weight: 501.477
• European Community (EC) Number: 634-317-6,639-451-9
• UNII: U6Q8Z01514
• DSSTox Substance ID: DTXSID5046487
• Nikkaji Number: J592.477D
• Wikidata: Q28851735
• NCI Thesaurus Code: C28811
• RXCUI: 141400
• Metabolomics Workbench ID: 43025
• ChEMBL ID: CHEMBL922
• Mol file: 142340-99-6.mol

Synonyms:9-(2-((-bis((pivaloyloxy)methoxy)phosphinyl)methoxy)ethyl)adenine;adefovir depivoxil;adefovir dipivoxil;GS 840;GS-0840;Hepsera;Preveon

Chemical Property of Adefovir dipivoxil

Chemical Property:

• Appearance/Colour: It has broad-spectrum antiviral activity
• Vapor Pressure: 2.52E-16mmHg at 25°C
• Melting Point: 98-102 °C
• Refractive Index: 1.569
• Boiling Point: 641 °C at 760 mmHg
• PKA: 4.16±0.10(Predicted)
• Flash Point: 341.5 °C
• PSA: 176.79000
• Density: 1.35 g/cm³
• LogP: 3.28370
• Storage Temp.: −20°C
• Solubility.: ethanol: soluble50mg/mL
• XLogP3: 1.8
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 12
• Rotatable Bond Count: 15
• Exact Mass: 501.19884999
• Heavy Atom Count: 34
• Complexity: 706

Purity/Quality:

99.5%min ^*data from raw suppliers

Adefovir Dipivoxil ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36/37

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)(C)C(=O)OCOP(=O)(COCCN1C=NC2=C(N=CN=C21)N)OCOC(=O)C(C)(C)C
• Recent ClinicalTrials: Study Comparing the Safety of Switching From Lamivudine to Adefovir Dipivoxil Versus Overlapping Lamivudine and Adefovir Before Adefovir Dipivoxil Monotherapy in Patients With Chronic Hepatitis B
• Recent EU Clinical Trials: A multicentre randomized controlled trial evaluating the rate of sustained remission and the safety when stopping nucleos(t)ide analogue treatment in non-cirrhotic HBeAg-negative chronic Hepatitis B patients with long-term virologic response
• Recent NIPH Clinical Trials: Effect of nucleosid analog and peginterferon alfa 2a sequential therapy on patients with chronic hepatitis B
• Uses: Has a broad spectrum of antiviral activity, can be used for the treatment of chronic hepatitis B. Adefovir Dipivoxil(Preveon, Hepsera) works by blocking reverse transcriptase, an enzyme that is crucial for the hepatitis B virus (HBV) to reproduce in the body. It is approved for the treatment of chronic hepatitis B in adults with evidence of active vir A nucleotide analog, useful as an oral reverse transcriptase inhibitor (ntRTI).
• Description: Adefovir dipivoxil is the first nucleotide analog to be launched in the US as an oral treatment for hepatitis B virus (HBV) infections. It can be easily prepared in 4 steps from adenine. Adefovir dipivoxil acts as a bioavailable ester prodrug which is rapidly hydrolyzed to free adefovir and further anabolized to its active form, adefovir diphosphate, by two intracellular phosphotylation steps. The diphosphate competitively inhibits reverse transcriptase and/or causes chain termination when incorporated into growing DNA. Adefovir dipivoxil has a broad antiviral spectrum against retro-, herpes- and hepadnaviruses. The drug inhibits HBV replication, decreases HBV DNA levels and improves liver histology of patients infected with HBV wild type and resistant to other antivirals such as lamivudine. It also demonstrated activity in hepatitis B”e” antigennegative, or precore mutant, patients and in patients co-infected with HIV. To date, no adefovir dipivoxil-associated resistance mutations have been identified in patients up to 136 weeks with the drug. The oral bioavailability of adefovir after oral administration of its dipivoxil prodrug is approximately 30%. It is mainly excreted unchanged in the urine and its plasma elimination half-life is 4.2 h. However, a long intracellular half-life (17 h) of the active bisphosphorylated metabolite enables once-daily dosing. The most prominent adverse effect of adefovir dipivoxil is nephrotoxicity (which has prevented the drug from being marketed for HIV infections where the drug required administration at higher doses).
• Clinical Use: Adefovir dipivoxil joins interferon and lamivudine in the treatment of chronic HBV. It can be used singly or in combination with lamivudine. Early clinical studies indicate benefit of the use of adefovir dipivoxil to treat lamivudine-resistant HBV with a low level of resistant virus developing to monotherapy with adefovir dipivoxil.
• Drug interactions: Potentially hazardous interactions with other drugs Use with caution in combination with other nephrotoxins. Antivirals: avoid concomitant administration with tenofovir Interferons: use with caution with peginterferon alfa.

Technology Process of Adefovir dipivoxil

There total 17 articles about Adefovir dipivoxil 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: 78.1%

Chloromethyl pivalate (18997-19-8) + Adefovir (106941-25-7) → adefovir dipivoxyl (142340-99-6)

Guidance literature:

With triethylamine; In 1-methyl-pyrrolidin-2-one; at 50 - 55 ℃; Solvent; Reagent/catalyst; Temperature; Inert atmosphere; Large scale;

Reference yield: 46.18%

[[2-chloroethoxy]methyl]phosphonic acid bis(pivaloyloxymethyl) ester + 7H-purin-6-ylamine (73-24-5,71660-29-2,71660-30-5) → adefovir dipivoxyl (142340-99-6)

Guidance literature:

With potassium carbonate; In N,N-dimethyl-formamide; at 90 - 95 ℃; for 9h; Large scale;

Reference yield: 43.0%

HOCH2OOCC(CH3)3 + 9-<2-(phosphonomethoxy)ethyl>adenine, bis(phenyl ester) (142341-24-0) → adefovir dipivoxyl (142340-99-6)

Guidance literature:

With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 20 ℃; for 16h;

upstream raw materials:

Chloromethyl pivalate

Adefovir

iodomethyl pivaloate

N⁶-(4-monomethoxytrityl)-9-(2-phosphonomethoxyethyl)adenine

Downstream raw materials:

Adefovir

Refernces

• 1、 -. "Preparation method of high-stability adefovir dipivoxil". Paragraph 0020; 0051; 0054; 0055; 0057; 0060; 0061. . Retrieved 2019/08/30.
• 2、 -. "Preparation method of adefovir dipivoxil". Paragraph 0048; 0049. . Retrieved 2019/04/02.