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

• ChemBase编号: 599
• 分子式: C20H32N5O8P
• 平均质量: 501.470541
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: [({[2-(6-amino-9H-purin-9-yl)ethoxy]methyl}({[(2,2-dimethylpropanoyl)oxy]methoxy})phosphoryl)oxy]methyl 2,2-dimethylpropanoate
• IUPAC传统名: adefovir dipivoxil
• 商标名: Hepsera; Preveon
• 别名: 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

登记号

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

理论计算性质

JChem

• Acid pKa: 18.58806
• 质子受体: 8
• 质子供体: 1
• LogD (pH = 5.5): 2.906959
• LogD (pH = 7.4): 3.0561967
• Log P: 3.058481
• 摩尔折射率: 119.9922 cm^3
• 极化性: 48.002186 Å^3
• 极化表面积: 166.98 Å^2
• 可自由旋转的化学键: 15
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 1.49
• LOG S: -2.9
• 溶解度: 6.33e-01 g/l

分子性质

理化性质

• 溶解度: 19 mg/mL at pH 2.0 and 0.4 mg/mL at pH 7.2.; DMSO
• 外观: White Solid
• 熔点: 101-103°C
• 疏水性(logP): 0.8

安全信息

• 保存条件: -20°C; Refrigerator
• 欧盟危险性物质标志: 有害性(Harmful) (Xn)
• 德国WGK号: 3
• 危险公开号: 20/21/22
• 安全公开号: 36/37
• GHS危险品标识: GHS07
• GHS警示词: Warning
• GHS危险声明: H302-H312-H332
• GHS警示性声明: P280
• 个人保护装置: dust mask type N95 (US), Eyeshields, Gloves
• 保存温度: -20°C

产品相关信息

• 成盐信息: Free Base
• Empirical Formula (Hill Notation): C20H32N5O8P

详细说明

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).

参考文献

• 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)