Tenofovir CAS:147127-20-6 Basic information
|Synonyms:||Tenofovir alafenamide-24;TENOFOVIR ALAFENAMIDE-24;(R)-(1-(6-aMino-9H-purin-9-yl)propan-2-yloxy)Methylphosphonic acid;Tenofovir (PMPA);Tenofovir(Viread);[[(1R)-2(6-AMino-9H-purin-9-yl)-1-Methylethoxy]Methyl]ph;Viread;1-(6-AMinopurin-9-yl)propan-2-yloxyMeth|
|Product Categories:||Inhibitors;Purine;ACTIVE PHARMACEUTICAL INGREDIENTS;Nucleotides and Nucleosides;Bases & Related Reagents;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals;Phosphorylating and Phosphitylating Agents|
Tenofovir CAS:147127-20-6 Chemical Properties
|Boiling point:||616.1±65.0 °C(Predicted)|
|storage temp.:||Store at -20°C|
|Water Solubility:||13.4 mg/mL (25 ºC)|
|PH:||D +21° (c = 1 in 0.1M HCl)|
|alpha:||D +21° (c = 1 in 0.1M HCl)|
|optical activity:||[α]20/D 1.50 to 0.0°, neat|
|CAS DataBase Reference:||147127-20-6(CAS DataBase Reference)|
White to off-white powder
供试样品 HPLC 图谱中主峰保留时间必须和标
The retention time of the major peak should be corresponding to the standard.
比旋度[a]20/D Specific rotation
-19°~ -23°，c = 0.5% 0.1 M HCl
色谱纯度Chromatographic purity (HPLC)
Any single impurity
结 论 ：
Complies as per above specification
|Tenofovir Usage And Synthesis|
|Indications and Usage||Tenofovir disoproxil (Viread) is the first nucleotide analogue approved by the American FDA to treat HIV-1 infections. Tenofovir disoproxil is a drug used in the AIDS cocktail treatment method, and research shows that it has the ability to increase monkeys’ immunity to immunodeficiency viruses (similar to the human AIDS virus). Tenofovir disoproxil is used in combination with other reverse transcriptase inhibitors to treat HIV-1 infections and hepatitis B.|
|Mechanisms of Action||Tenofovir disoproxil is an acyclic nucleoside antivirus drug and has an inhibiting effect on HBV multi-enzyme complexes and HIV reverse transcriptase. Its active content tenofovir phosphonate directly competitively binds to natural deoxyribose substrate to inhibit the virus multi-enzyme complex and inserts itself into the DNA to end the nucleotide chain. Tenofovir disoproxil is barely absorbed by the gastrointestinal duct, so it undergoes esterification and ionization to become tenofovir ester fumarate. Tenofovir is soluble in water and can be quickly absorbed and decomposed into the active substance tenofovir, which then transforms into the active metabolite tenofovir phosphonate. As this drug is not metabolized by the CYP450 enzyme system, it has a very low chance of drug interactions caused by this enzyme.|
|Pharmacokinetics||Tenofovir disoproxil reaches peak blood concentration 1-2 hours after intake. Tenofovir disoproxil’s bioavailability increases by about 40% when taken with food. The intracellular half-life of tenofovir phosphonate is about 10 hours, so doses can be taken once daily. This drug is mainly filtered through renal glomeruli and excreted through the renal tubule transport system, with 70-80% excreted in its original form through urine.|
|Chemical Properties||White Crystalline Solid|
|Uses||Tenofovir is a drug used for the treatment of chronic heptatitis B as well as prevention and treatment of HIV/AIDS. It is a kind of nucleotide analog, acting as the reverse-transcriptase inhibitor (NtRTI). It inhibits the activity of HIV reverse transcriptase through competing with the natural substrate deoxyadenosine 5’-triphosphate, causing the termination of DNA chain.|
|Definition||ChEBI: A member of the class of phosphonic acids that is methylphosphonic acid in which one of the methyl hydrogens is replaced by a [(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy group. An inhibitor of HIV-1 reverse transcriptase, the bis(isopropyloxycarbonyloxy ethyl) ester (disoproxil ester) prodrug is used as the fumaric acid salt in combination therapy for the treatment of HIV infection.|
|Indications||Tenofovir disoproxil fumarate (Viread) is a prodrug of tenofovir, a phosphorylated adenosine nucleoside analogue, and is the only available agent of its class. It is converted by cellular enzymes to tenofovir diphosphate, which competes with deoxyadenosine triphosphate (dATP) for access to reverse transcriptase and causes chain termination following its incorporation. Tenofovir was approved as part of a combination therapy for HIV in adults who failed treatment with other regimens; it appears to be effective against HIV strains that are resistant to NRTIs.|
|Acquired resistance||HIV variants with the K65R mutation and the K70E mutation in the reverse transcriptase demonstrate reduced susceptibility to tenofovir.|
|Pharmaceutical Applications||A nucleotide analog structurally similar to adefovir.|
EC50 values for HBV, assessed in the HepG2 2.2.15 cell line, ranged from 0.14 to 1.5 μm; the cytotoxic concentration exceeded 100 μm. A decline in HBV DNA levels below 105 copies/mL at 48 weeks of therapy in 100% of patients receiving tenofovir compared with 44% on adefovir therapy has been reported. There are also case reports of patients with primary resistance to adefovir responding to tenofovir.
It is generally well tolerated in patients with chronic HBV; the most common side effects include nausea and gastrointestinal upset, headache, dizziness, fatigue and rash.
|Pharmaceutical Applications||An acyclic nucleoside phosphonate, formulated as the disoproxil fumarate salt for oral administration.|
|Biological Activity||Selectively inhibits HIV reverse transcriptase (RNA-dependent DNA polymerase). Prevents cytotoxicity in SIV-infected C-8166 cells in vitro (IC 50 = 1.5 μ M). Antiviral agent.|
|Pharmacokinetics||Oral absorption: c. 25%|
Cmax 300 mg once daily: 0.3 mg/L
Plasma half-life: 17 h
Volume of distribution: 1.3 ± 0.6 L/kg at 3.0 mg/kg intravenous dose
Plasma protein binding: <0.7% (in vitro)
Absorption and distribution
Oral bioavailability is poor, but is enhanced by administration as the disoproxil prodrug. It may be taken with or without food. CSF penetration is likely to be minimal due to the anionic charge of the molecule at physiological pH. It accumulates in semen at higher concentrations than in plasma. It is not known if it is distributed into breast milk.
Metabolism and excretion
Tenofovir is not metabolized and is principally eliminated by the kidneys by a combination of glomerular filtration and active tubular secretion. In patients with renal dysfunction the dose should be adjusted accordingly.
Compounds such as cidofovir, aciclovir (acyclovir), valaciclovir, ganciclovir, valganciclovir and probenecid may compete for renal excretion. Tenofovir levels are increased when prescribed with some HIV protease inhibitors. The co-administration of tenofovir with didanosine leads to didanosine accumulation which is thought to occur through inhibition of purine nucleoside phosphorylase. This has been associated with impaired immune recovery and several cases of lactic acidosis and pancreatitis. If tenofovir is combined with didanosine the dose of didanosine should be reduced to 200 mg (<60 kg) or 250 mg (≥60 kg) per day and the patient monitored for symptoms of didanosine toxicity.
|Clinical Use||Chronic hepatitis B infection|
|Clinical Use||Treatment of HIV infection in adults and children (in combination with other antiretroviral drugs)|
|Side effects||In clinical trials of antiretroviral treatment-naive participants, the most commonly reported adverse events were mild to moderate gastrointestinal upset (nausea 8%, diarrhea 11%), headache (14%) and depression (11%). Tenofovir has the potential to result in nephrotoxicity, particularly through proximal tubular damage, but the risk of clinically significant renal dysfunction appears relatively low and seems to occur mainly in subjects with other identifiable risks for renal impairment. Minor elevations in serum creatinine and reductions in creatinine clearance occur, but rarely require drug discontinuation.|
A few (<0.1%) cases of osteomalacia and decreased bone density have been reported.
|Side effects||Tenofovir is taken once daily and is generally well tolerated, perhaps because it produces less mitochondrial toxicity than the NRTIs. Nausea, vomiting, flatulence, and diarrhea occur in 10% or fewer patients. Resistance to tenofovir has been documented, and cross-resistance to NRTIs may occur.|