Adefovir Dipivoxil
ADEFOVIR · Hepsera · Adefovir Dipivoxi · Preveon · GS 0840 · Ade Vove · adefuweizhi · C20H32N5O8P
Identifikatoren & physikalische Daten
| CAS No. | 142340-99-6 |
|---|---|
| Summenformel | C20H32N5O8P |
| Durchschnittliche Molmasse | 501,5 g/mol |
| Monoisotopische Masse | 501,19884961 g/mol |
| SMILES | CC(C)(C)C(=O)OCOP(=O)(COCCn1cnc2c(N)ncnc21)OCOC(=O)C(C)(C)C |
| InChIKey | WOZSCQDILHKSGG-UHFFFAOYSA-N |
| PubChem CID | 60871 |
| ChEMBL | CHEMBL922 |
| ChEBI | CHEBI:31175 |
| EC No. | 634-317-6 |
| DTXSID | DTXSID5046487 |
Chemische & physikalische Eigenschaften
| XLogP | 1,8 |
|---|---|
| Polarare Oberfläche (TPSA) | 167 |
| H-Brücken-Donoren | 1 |
| H-Brücken-Akzeptoren | 12 |
| Frei drehbare Bindungen | 15 |
| Schwere Atome | 34 |
| Formalladung | 0 |
| Komplexität | 705 |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15 |
| LogP (Verteilungskoeffizient) | 0.82.48 |
| Löslichkeit | 6.33e-01 g/Lethanol: soluble50mg/mL |
| Human Drugs | FDA approved drugs -> Active ingredient |
| Physical Description | Solid |
| Schmelzpunkt | 98-102°C |
| Siedepunkt | 641.0±65.0 °C(Predicted) |
| Dichte | 1.35±0.1 g/cm3(Predicted) |
| Lagerbedingungen | Keep in dark place,Inert atmosphere,Store in freezer, under -20°C |
| pKa (Säurekonstante) | 4.16±0.10(Predicted) |
| Aggregatzustand | solid |
| Farbe | White to Off-White |
| Biologische Quelle | synthetic |
| Merck | 14,151 |
| InChI | InChI=1S/C20H32N5O7P/c1-19(2,3)17(26)29-11-31-33(32-12-30-18(27)20(4,5)6)13-28-8-7-25-10-24-14-15(21)22-9-23-16(14)25/h9-10H,7-8,11-13H2,1-6H3,(H2,21,22,23) |
| InChIKey | WOZSCQDILHKSGG-UHFFFAOYSA-N |
| SMILES | P(OCOC(=O)C(C)(C)C)(OCOC(=O)C(C)(C)C)COCCN1C2C(N=C1)=C(N)N=CN=2 |
| CAS Datenbank | 142340-99-6(CAS DataBase Reference) |
Sicherheit & Vorschriften
| GHS-Einstufung | WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P261, P264, P270, P271, P280, P301+P317, P302+P352, P304+P340, P317, P321, P330, P362+P364, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 41 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Danger |
|---|---|
| Hazard Classes and Categories | Acute Tox. 4 (100%) |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)Adefovir dipivoxilvLess-DILI-concernWarnings & precautionsDOI:10.1016/j.drudis.2016.02.015 |
| Wassergefährdungsklasse (WGK) | 3 |
| Zollcode | 2933.99.8290 |
| RTECS-Nr. | UA2459362 |
| R-Sätze (R) | 20/21/22 |
| Gefahrensymbole | Xn |
| Sicherheitshinweise (S) | 36/37 |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrenklasse | Acute Tox. 4 Oral |
Anwendungen & Verwendung
Beschreibung
Adefovir dipivoxil is the first nucleotide analog to be launched in the US as an oral treatment for hepatitis B virus (HBV) infections. It can be easily prepared in 4 steps from adenine. Adefovir dipivoxil acts as a bioavailable ester prodrug which is rapidly hydrolyzed to free adefovir and further anabolized to its active form, adefovir diphosphate, by two intracellular phosphotylation steps. The diphosphate competitively inhibits reverse transcriptase and/or causes chain termination when incorporated into growing DNA. Adefovir dipivoxil has a broad antiviral spectrum against retro-, herpes- and hepadnaviruses. The drug inhibits HBV replication, decreases HBV DNA levels and improves liver histology of patients infected with HBV wild type and resistant to other antivirals such as lamivudine. It also demonstrated activity in hepatitis B”e” antigennegative, or precore mutant, patients and in patients co-infected with HIV. To date, no adefovir dipivoxil-associated resistance mutations have been identified in patients up to 136 weeks with the drug. The oral bioavailability of adefovir after oral administration of its dipivoxil prodrug is approximately 30%. It is mainly excreted unchanged in the urine and its plasma elimination half-life is 4.2 h. However, a long intracellular half-life (17 h) of the active bisphosphorylated metabolite enables once-daily dosing. The most prominent adverse effect of adefovir dipivoxil is nephrotoxicity (which has prevented the drug from being marketed for HIV infections where the drug required administration at higher doses).
Verwenden
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 vir