Tenofovir
(R)-9-(2-Phosphonomethoxypropyl)Adenine · (R)-9-(2-PHOSPHONYLMETHOXYPROPYL)-ADENINE · Viread · GS-1278 · Apropovir · 9-Pmpa · GS 1275 · (R)-PMPA
Identifikatoren & physikalische Daten
| CAS No. | 147127-20-6 |
|---|---|
| Summenformel | C9H14N5O4P |
| Durchschnittliche Molmasse | 287,21 g/mol |
| Monoisotopische Masse | 287,07834056 g/mol |
| SMILES | C[C@H](Cn1cnc2c(N)ncnc21)OCP(=O)(O)O |
| InChIKey | SGOIRFVFHAKUTI-ZCFIWIBFSA-N |
| PubChem CID | 464205 |
| ChEMBL | CHEMBL3989702 |
| ChEBI | CHEBI:63625 |
| EC No. | 604-571-2 |
| DTXSID | DTXSID9040132 |
Chemische & physikalische Eigenschaften
| XLogP | -1,6 |
|---|---|
| Polarare Oberfläche (TPSA) | 136 |
| H-Brücken-Donoren | 3 |
| H-Brücken-Akzeptoren | 8 |
| Frei drehbare Bindungen | 5 |
| Schwere Atome | 19 |
| Formalladung | 0 |
| Komplexität | 354 |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Metabolite of Tenofovir alafenamide, 'Tenofovir disoproxil |
| LogP (Verteilungskoeffizient) | -1.6 |
| Löslichkeit | 1.87e+00 g/LAqueous Acid (Sparingly), DMSO (Slightly, Heated), Water (Slightly, Heated)13.4 mg/mL (25 ºC) |
| Human Drugs | FDA approved drugs -> Active ingredient |
| Schmelzpunkt | 276 - 280 °C276-280°C |
| Physical Description | Solid |
| Dissociation Constants | 3.8 and 6.7 |
| Siedepunkt | 616.1±65.0 °C(Predicted) |
| Dichte | 1.79±0.1 g/cm3(Predicted) |
| Lagerbedingungen | -20°C |
| pKa (Säurekonstante) | 2.36±0.10(Predicted) |
| Aggregatzustand | powder |
| Farbe | white to beige |
| Merck | 14,9146 |
| InChI | InChI=1S/C9H14N5O4P/c1-6(18-5-19(15,16)17)2-14-4-13-7-8(10)11-3-12-9(7)14/h3-4,6H,2,5H2,1H3,(H2,10,11,12)(H2,15,16,17)/t6-/m1/s1 |
| InChIKey | SGOIRFVFHAKUTI-ZCFIWIBFSA-N |
| SMILES | P(CO[C@H](C)CN1C2C(N=C1)=C(N)N=CN=2)(=O)(O)O |
| CAS Datenbank | 147127-20-6(CAS DataBase Reference) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH318 (100%): Causes serious eye damage [Danger Serious eye damage/eye irritation]P264+P265, P280, P305+P354+P338, and P317 (click each P-code to see the statement)Aggregated GHS information provided per 2 reports by companies from 1 notifications to the ECHA C&L Inventory. |
|---|---|
| Regulatorische Informationen | Status: Active Update: 28-04-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/10529 |
| Hazard Classes and Categories | Eye Dam. 1 (100%) |
| Hepatotoxicity | Like all nucleoside analogues used as therapy of hepatitis B, tenofovir can cause transient increases in serum aminotransferases during or after therapy. These abnormalities appear to be due to an exacerbation or flare of the underlying hepatitis B. Three types of flares due to nucleoside analogue therapy have been described: transient flares during initiation of therapy (treatment flares), flares occurring in association with development of antiviral resistance (breakthrough flares) and flares occurring in the few months after stopping therapy (withdrawal flares). Treatment flares generally arise during the first few months of starting therapy, are usually mild, asymptomatic and self-limited and do not require dose modification or interruption of therapy. Breakthrough flares generally follow the development of antiviral resistance and subsequent rise in HBV DNA levels during nucleoside analogue therapy. Breakthrough flares can be symptomatic and severe. Because tenofovir is associated with a very low rate of antiviral resistance ( |
| Drug Induced Liver Injury | Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)tenofovirViread®Antivirals8most-DILI-concern |
| Wassergefährdungsklasse (WGK) | WGK 3 |
| Zollcode | 29339900 |
| RTECS-Nr. | SZ6563600 |
| Lagerklasse | 11 - Combustible Solids |
Anwendungen & Verwendung
Beschreibung
Tenofovir is an analog of adenosine monophosphate that has antiviral activity. It is converted by cellular enzymes to tenofovir diphosphate, an obligate chain terminator that inhibits the activity of HIV reverse transcriptase and hepatitis B virus polymerase. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases α and β and mitochondrial DNA polymerase γ. For in vivo and cell culture use, tenofovir is supplied as a water soluble prodrug in the form of tenofovir disoproxil (fumarate) , which increases the intracellular diphosphorylated compound >1,000-fold above the level attained with unmodified tenofovir.
History
Tenofovir was developed in the 1980s by Professor Antonín Holý and his team at the Institute of Organic Chemistry and Biochemistry (IOCB Prague) of the Czech Academy of Sciences. Their research focused on the design and synthesis of nucleotide analogs, aiming to develop novel compounds with antiviral activity. As an acyclic nucleotide phosphate analog, tenofovir exhibited broad-spectrum antiviral potential in vitro, but its low oral bioavailability limited its initial development. To overcome this bottleneck, collaboration with Gilead Sciences was crucial, ultimately leading to the successful development of tenofovir disoproxil fumarate (TDF) through a prodrug synthesis strategy. This prodrug was first approved by the FDA in 2001 for the treatment of HIV-1 infection, marking a significant breakthrough in its clinical application. Subsequent research further solidified its position in the treatment of chronic hepatitis B and facilitated the market launch of tenofovir alafenamide (TAF), a prodrug with superior renal and bone safety characteristics.
Verwenden
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.