Adefovir Dipivoxil
ADEFOVIR · Hepsera · Adefovir Dipivoxi · Preveon · GS 0840 · Ade Vove · adefuweizhi · C20H32N5O8P
Identifiers & Physical Properties
| CAS No. | 142340-99-6 |
|---|---|
| Molecular formula | C20H32N5O8P |
| Average molar mass | 501.5 g/mol |
| Monoisotopic mass | 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 |
Chemical & Physical Properties
| XLogP | 1.8 |
|---|---|
| Topological polar surface area | 167 |
| Hydrogen bond donors | 1 |
| Hydrogen bond acceptors | 12 |
| Rotatable bonds | 15 |
| Heavy atoms | 34 |
| Formal charge | 0 |
| Complexity | 705 |
| Drugs | Pharmaceuticals -> Listed in ZINC15 |
| LogP (partition coefficient) | 0.82.48 |
| Solubility | 6.33e-01 g/Lethanol: soluble50mg/mL |
| Human Drugs | FDA approved drugs -> Active ingredient |
| Physical Description | Solid |
| Melting point | 98-102°C |
| Boiling point | 641.0±65.0 °C(Predicted) |
| Density | 1.35±0.1 g/cm3(Predicted) |
| Storage conditions | Keep in dark place,Inert atmosphere,Store in freezer, under -20°C |
| pKa (acidity coefficient) | 4.16±0.10(Predicted) |
| Physical state | solid |
| Color | White to Off-White |
| Biological source | 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 DataBase Reference | 142340-99-6(CAS DataBase Reference) |
| FDA UNII | U6Q8Z01514 |
| NCI Drug Dictionary | adefovir dipivoxil |
| ATC code | J05AF08 |
| UNSPSC Code | 51102829 |
| NACRES | NA.76 |
| Protein binding | <4% |
| Excreted unchanged in urine | 45% |
| Volume of distribution | 0.4(L/kg) |
| Biological half-life | 7 / 15 |
| GHS pictogram | GHS07 |
| Signal word | Warning |
| GHS hazard statements | H302+H312+H332 |
| GHS precautionary statements | P261-P264-P280-P301+P312-P302+P352+P312-P304+P340+P312 |
| Personal protective equipment (PPE) | dust mask type N95 (US), Eyeshields, Gloves |
| Hazard symbols | Xn |
| Risk statements (R) | 20/21/22 |
| Safety statements (S) | 36/37 |
| Water hazard class (WGK) | 3 |
| RTECS number | UA2459362 |
| Customs code | 2933.99.8290 |
| Storage class | 11 - Combustible Solids |
| Hazard class | Acute Tox. 4 Oral |
Safety & Regulations
| GHS classification | 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 |
| Personal protective equipment (PPE) | dust mask type N95 (US), Eyeshields, Gloves |
| Water hazard class (WGK) | 3 |
| RTECS number | UA2459362 |
| Customs code | 2933.99.8290 |
| Risk statements (R) | 20/21/22 |
| Signal word | Warning |
| GHS pictogram | GHS07 |
| Hazard symbols | Xn |
| Safety statements (S) | 36/37 |
| Storage class | 11 - Combustible Solids |
| GHS hazard statements | H302+H312+H332 |
| Hazard class | Acute Tox. 4 Oral |
| GHS precautionary statements | P261-P264-P280-P301+P312-P302+P352+P312-P304+P340+P312 |
Applications & Uses
Uses
Has a broad spectrum of antiviral activity, can be used for the treatment of chronic hepatitis B.
Description
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).
Uses
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
Uses
A nucleotide analog, useful as an oral reverse transcriptase inhibitor (ntRTI).
General Description
Adefovir is an orally active prodrug that is indicated for thetreatment of the chronic form of hepatitis B. The dipivoxil moieties are hydrolyzed by ubiquitous esterases to yieldadefovir, which is phosphorylated by adenylate kinase toyield adefovir diphosphate. This compound is inhibitory atHBV DNA polymerase. In addition, adefovir undergoes incorporationinto viral DNA and causes chain termination.Adefovir is poorly absorbed by the oral route, but the dipivoxilester groups cause the bioavailability to increase toapproximately 60%.