106941-25-7

Pale Brown Solid

Used as an antiviral

ChEBI: Adefovir is a member of the class of phosphonic acids that is methylphosphonic acid in which one of the methyl hydrogens has been replaced by a 2-(6-amino-9H-purin-9-yl)ethoxy group. An inhibitor of HIV-1 reverse transcriptase, the bis(t-butoxycarbonyloxymethyl) ester (dipivoxil ester) prodrug is used to treat chronic hepatitis B viral infection. It has a role as a HIV-1 reverse transcriptase inhibitor, a drug metabolite, an antiviral drug, a nephrotoxic agent and a DNA synthesis inhibitor. It is a member of 6-aminopurines, an ether and a member of phosphonic acids. It is functionally related to an adenine. It is a conjugate acid of an adefovir(1-).

It has a lower propensity to induce drug resistance than lamivudine. Clinical trials of patients receiving 48 weeks of therapy did not identify any cases of resistance. Longer courses yield resistant strains of HBV with mutations in the DNA polymerase gene; other rare variants of resistant strains have been identified. Lamivudine-resistant strains of HBV retain susceptibility to adefovir.

A nucleotide analog of adenosine monophosphate, administered orally as its prodrug, adefovir dipivoxil.

Adefovir is an antiviral drug that after intracellular conversion to adefovir diphosphate inhibits hepatitis B virus (HBV) DNA polymerase (reverse transcriptase).

Oral absorption： c. 60%
C_max 10 mg/kg oral： 18.4 ng/mL
Plasma half-life： c. 7.5 h.
Volume of distribution： 392 mL/kg
Plasma protein binding： Not known
The prodrug is metabolized to adefovir, which is excreted by the kidneys and therefore requires dose adjustment in patients with impaired renal function. It does not induce cytochrome P₄₅₀ at standard doses and does not influence the metabolism or plasma concentrations of the other licensed medications used in the treatment of hepatitis B.

Treatment of chronic hepatitis B virus infection in patients >12 years of age

It is generally well tolerated, with headache, pharyngitis, abdominal pain and peripheral neuropathy being the most common side effects. Nephrotoxicity has been observed in some patients, with those receiving higher doses and longer courses of therapy at greater risk. Exacerbation of hepatitis has been reported in patients immediately following discontinuation of treatment. Most exacerbations occur within 12 weeks of stopping therapy, and elevations of alanine aminotransferase (ALT) up to 10 times the upper limit of normal can be observed in over 25% of patients. Lactic acidosis has been reported in a few patients and is an indication for immediate discontinuation.

The general procedure for the synthesis of ((2-(6-amino-9H-purin-9-yl)ethoxy)methyl)phosphonic acid from diethyl ((2-(6-amino-9H-purin-9-yl)ethoxy)methyl)phosphonate is as follows: a 10L three-necked flask was fitted with a mechanical stirrer and thermometer. 1.4 kg (4.26 mol) of diethyl ((2-(6-amino-9H-purin-9-yl)ethoxy)methyl)phosphonate (Intermediate III) and 8 L of acetonitrile were sequentially added to the flask, followed by the addition of trimethylmethylsilyl bromide. The reaction mixture was stirred at room temperature for 1 hour and then heated to reflux for 2 hours. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. To the residue, 5 L of water was added, the mixture was stirred and the pH was adjusted to 3.2-3.4 with 25% sodium hydroxide solution. the mixture was heated to reflux for 2 hr. Upon completion of the reaction, the reaction mixture was cooled to room temperature and filtered. The filter cake was purified by aqueous recrystallization and dried under vacuum at 70 °C for 8 h. 9-(2-phosphomethoxyethyl)adenine was obtained as a white crystalline solid powder with a yield of 1.07 kg, 86.3% yield and melting point of 298-300 °C.

Store at -20°C