[({[2-(6-amino-9H-purin-9-yl)ethoxy]methyl}({[(2,2-dimethylpropanoyl)oxy]methoxy})phosphoryl)oxy]methyl 2,2-dimethylpropanoate

• ChemBase ID: 599
• Molecular Formular: C20H32N5O8P
• Molecular Mass: 501.470541
• Monoisotopic Mass: 501.19884964
• SMILES: P(=O)(OCOC(=O)C(C)(C)C)(OCOC(=O)C(C)(C)C)COCCn1c2ncnc(N)c2nc1
• Canonical SMILES: O=C(C(C)(C)C)OCOP(=O)(OCOC(=O)C(C)(C)C)COCCn1cnc2c1ncnc2N
• InChI: InChI=1S/C20H32N5O8P/c1-19(2,3)17(26)30-11-32-34(28,33-12-31-18(27)20(4,5)6)13-29-8-7-25-10-24-14-15(21)22-9-23-16(14)25/h9-10H,7-8,11-13H2,1-6H3,(H2,21,22,23)
• InChIKey: WOZSCQDILHKSGG-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: [({[2-(6-amino-9H-purin-9-yl)ethoxy]methyl}({[(2,2-dimethylpropanoyl)oxy]methoxy})phosphoryl)oxy]methyl 2,2-dimethylpropanoate
• IUPAC Traditional name: adefovir dipivoxil
• Brand Name: Hepsera; Preveon
• Synonyms: 9-(2[bis(Pivaloyloxymethoxy)phosphorylmethoxy]ethyl)adenine; Adefovir dipivoxil; Adefovirdipivoxl; Adefovir pivoxil; Adefovir; ADV; bis-POM PMEA; PMEA; adefovir dipivoxil; GS-840; Adefovir Dipivoxil; 2,2-Dimethyl-propanoic Acid 1,1'-[[[[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphinylidene]bis(oxymethylene)] Ester; bis(POM)-PMEA; Preveon; Hepsera

Database IDs

• CAS Number: 142340-99-6
• MDL Number: MFCD00869897
• PubChem SID: 46507520; 160964062
• PubChem CID: 60871

CALCULATED PROPERTIES

JChem

• Acid pKa: 18.58806
• H Acceptors: 8
• H Donor: 1
• LogD (pH = 5.5): 2.906959
• LogD (pH = 7.4): 3.0561967
• Log P: 3.058481
• Molar Refractivity: 119.9922 cm^3
• Polarizability: 48.002186 Å^3
• Polar Surface Area: 166.98 Å^2
• Rotatable Bonds: 15
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 1.49
• LOG S: -2.9
• Solubility (Water): 6.33e-01 g/l

PROPERTIES

Physical Property

• Solubility: 19 mg/mL at pH 2.0 and 0.4 mg/mL at pH 7.2.; DMSO
• Apperance: White Solid
• Melting Point: 101-103°C
• Hydrophobicity(logP): 0.8

Safety Information

• Storage Condition: -20°C; Refrigerator
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 20/21/22
• Safety Statements: 36/37
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302-H312-H332
• GHS Precautionary statements: P280
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves
• Storage Temperature: -20°C

Product Information

• Salt Data: Free Base
• Empirical Formula (Hill Notation): C20H32N5O8P

DETAILS

DrugBank - DB00718

• Drug Groups: approved; investigational
• Description: Adefovir dipivoxil, previously called bis-POM PMEA, with trade names Preveon and Hepsera, is an orally-administered nucleotide analog reverse transcriptase inhibitor (ntRTI) used for treatment of hepatitis B. It is a failed treatment for HIV. [Wikipedia]
• Indication: For the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
• Pharmacology: Adefovir dipivoxil a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV). The concentration of adefovir that inhibited 50% of viral DNA synthesis (IC50) in vitro ranged from 0.2 to 2.5 μM in HBV transfected human hepatoma cell lines. The combination of adefovir with lamivudine showed additive anti-HBV activity.
• Toxicity: Renal tubular nephropathy characterized by histological alterations and/or increases in BUN and serum creatinine was the primary dose-limiting toxicity associated with administration of adefovir dipivoxil in animals. Nephrotoxicity was observed in animals at systemic exposures approximately 3–10 times higher than those in humans at the recommended therapeutic dose of 10 mg/day.
• Affected Organisms: Hepatitis B virus
• Biotransformation: Following oral administration, adefovir dipivoxil is rapidly converted to adefovir. Forty-five percent of the dose is recovered as adefovir in the urine over 24 hours at steady state following 10 mg oral doses. Adefovir is not a substrate of the cytochrome P450 enzymes.
• Absorption: Approximate oral bioavailability is 59%.
• Half Life: Terminal elimination half-life of 7.48 ± 1.65 hours
• Protein Binding: ≤4% over the adefovir concentration range of 0.1 to 25 μg/mL
• Elimination: Adefovir is renally excreted by a combination of glomerular filtration and active tubular secretion.
• Distribution: * 392 ± 75 mL/kg [intravenous administration of 1.0 mg/kg/day]; * 352 ± 9 mL/kg [intravenous administration of 3.0 mg/kg/day]
• Clearance: * 469 +/- 99.0 mL/min [Patients with Unimpaired renal Function receiving a 10 mg single dose]; * 356 +/- 85.6 mL/min [Patients with mild renal impairement receiving a 10 mg single dose]; * 237 +/- 118 mL/min [Patients with moderate renal impairement receiving a 10 mg single dose]; * 91.7+/- 51.3 mL/min [Patients with severe renal impairement receiving a 10 mg single dose]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1718

Research Area: Infection
Biological Activity:
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 viral replication and either evidence of persistent elevations in serum aminotransferases (primarily ALT) or histologically active disease. [1]

Sigma Aldrich - A9730

Biochem/physiol Actions
Antiviral acyclic nucleoside phosphonate (ANP) analog.
Adefovir is an antiviral acyclic nucleoside phosphonate (ANP) analog.that works by blocking reverse transcriptase 3. It is an inhibitor of duck hepatitis B virus (DHBV) replication that inhibits covalently closed circular DNA (CCC DNA) amplification 4. Cytotxicity is induced by Human Renal Organic Anion Transporter 1 (hOAT1) 5. Adefovir is an Inhibitor of edema factor (EF)-induced cAMP accumulation and changes in cytokine production in mouse primary macrophages 2.
Application
Adefovir is used to treat hepatitis B infections. It is used to study organ-specific toxicity and immune mechanisms of Adefovir treatment 1,2.

Toronto Research Chemicals - A280465

A nucleotide analog, useful as an oral reverse transcriptase inhibitor (ntRTI).

REFERENCES

• http://en.wikipedia.org/wiki/Adefovir
• Fliri, A., et al.: J. Med. Chem., 52, 8038 (2009)
• Fourches, D., et al.: Chem. Res. Toxicol., 23, 171 (2009)
• Ming, X., et al.: Biochem. Pharmacol., 79, 455 (2009)