CAS 142340-99-6|bis-POM PMEA|Hepsera|Adefovir Dipivoxil|adefovir dipivoxil|[({[2-(6-amino-9H-purin-9-yl)ethoxy]methyl}({[(2,2-dimethylpropanoyl)oxy]methoxy})phosphoryl)oxy]methyl 2,2-dimethylpropano...

基本信息

化学结构

分子式

C₂₀H₃₂N₅O₈P

分子量

501.470541

精确质量

501.19884964

电荷

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

Canonic Smiles

O=C(C(C)(C)C)OCOP(=O)(OCOC(=O)C(C)(C)C)COCCn1cnc2c1ncnc2N

Isomeric Smiles

P(=O)(OCOC(=O)C(C)(C)C)(OCOC(=O)C(C)(C)C)COCCn1c2ncnc(N)c2nc1

计算属性

JChem

LogD (pH = 7.4)

3.06

LogD (pH = 5.5)

2.98

Log P

3.06

可自由旋转的化学键

质子供体

质子受体

里宾斯基五规则

false

Acid pKa

4.83

极化表面积

166.98

极化性

49.12

摩尔折射率

119.99

LOG S

-3.57

数据来源

名称和标识

别名

PreveonAdefovir DipivoxilHepserabis-POM PMEAAdefoviradefovir dipivoxilADVAdefovirdipivoxlGS-840Adefovir pivoxilPMEA9-(2[bis(Pivaloyloxymethoxy)phosphorylmethoxy]ethyl)adenineAdefovir dipivoxil2,2-Dimethyl-propanoic Acid 1,1'-[[[[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphinylidene]bis(oxymethylene)] Esterbis(POM)-PMEA(((2-(6-Amino-9H-purin-9-yl)ethoxy)methyl)phosphinylidene)bis(oxymethylene) 2,2-dimethylpropanoateAdefovir dipivoxilGS 840preveonGS-08409-(2-((-Bis((pivaloyloxy)methoxy)phosphinyl)methoxy)ethyl)adenineadefovir pivoxil9-(2-((Bis((pivaloyloxy)methoxy)phosphinyl)methoxy)ethyl)adenineGS 0840hepsera

IUPAC传统名

adefovir dipivoxil

IUPAC标准名

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

商标名

HepseraPreveon

名称和标识

数据登录号

CAS号

142340-99-6

MDL号

MFCD00869897

PubChem SID

16096406246507520329735912

PubChem CID

BindingDB数据库

KEGG DRUG Database

ACToR数据库

MetaboLights数据库

HMDB数据库

CHEBI ID

DrugBank ID

CompTox数据库

Drug Central Database

SureChEMBL数据库

SCHEMBL29729

Reaxys Registry

29413415

CHEMBL

CHEMBL922

数据登录号

化合物性质

产品相关信息

成盐信息

Free Base

Empirical Formula (Hill Notation)

C20H32N5O8P

质检报告

下载链接

化合物性质

分子相关蛋白质

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分子图谱

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描述信息

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.

TRC

A280465

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

ChEBI

CHEBI:31175

An organic phosphonate that is the dipivoxil ester of adefovir. A prodrug for adefovir, an HIV-1 reverse transcriptase inhibitor, adefovir pivoxil is used to treat chronic hepatitis B viral infection.

描述信息

参考文献

PubChem文献

数据源提供

• http://en.wikipedia.org/wiki/Adefovir

• Fourches, D., et al.: Chem. Res. Toxicol., 23, 171 (2009)

• Ming, X., et al.: Biochem. Pharmacol., 79, 455 (2009)

• Fliri, A., et al.: J. Med. Chem., 52, 8038 (2009)

参考文献

生物活性

PubChem BioAssay

生物活性