U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C9H12N6O3
Molecular Weight 252.23
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMDOXOVIR

SMILES

NC1=NC2=C(N=CN2[C@H]3CO[C@@H](CO)O3)C(N)=N1

InChI

InChIKey=RLAHNGKRJJEIJL-RFZPGFLSSA-N
InChI=1S/C9H12N6O3/c10-7-6-8(14-9(11)13-7)15(3-12-6)4-2-17-5(1-16)18-4/h3-5,16H,1-2H2,(H4,10,11,13,14)/t4-,5-/m1/s1

HIDE SMILES / InChI
Molecular Formula C9H12N6O3
Molecular Weight 252.23
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800004771

Amdoxovir is a guanosine analogue nucleoside reverse transcriptase inhibitor that is active in vitro against both HIV-1 and HBV. It is deaminated intracellularly by adenosine deaminase to dioxolane guanine (DXG). DXG-triphosphate, the active form of the drug, has greater activity than DAPD-triphosphate. Amdoxovir is under development (phase II study) for the treatment of HIV infection. Five subjects demonstrated lens opacities during the study, although baseline evaluations were not performed. Clinical studies of amdoxovir are currently on hold pending additional safety data.

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 0.61 µM [IC50]
Substrate
661
Inhibitor
8504
 0.019 µM [Ki]
Inhibitor
8504
 32.0 µM [Ki]
Inhibitor
8504
 78.0 µM [Ki]
Inhibitor
8504
 4.3 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1545 ng/mL
REVIEW
https://pubmed.ncbi.nlm.nih.gov/20038617
500 mg 2 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
1,3-DIOXOLANE GUANOSINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
499 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20038617
500 mg 2 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMDOXOVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6834 ng × h/mL
REVIEW
https://pubmed.ncbi.nlm.nih.gov/20038617
500 mg 2 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
1,3-DIOXOLANE GUANOSINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1326 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20038617
500 mg 2 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMDOXOVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
17.6 h
REVIEW
https://pubmed.ncbi.nlm.nih.gov/20038617
500 mg 2 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
1,3-DIOXOLANE GUANOSINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1.4 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20038617
500 mg 2 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMDOXOVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
500 mg 2 times / day multiple, oral
Highest studied dose
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16184030
unhealthy
Health Status: unhealthy
Sex: M
Sources:
https://pubmed.ncbi.nlm.nih.gov/16184030
Sources:
https://pubmed.ncbi.nlm.nih.gov/16184030
Sourcing

Sourcing

Vendor/AggregatorIDURL
BOC Sciences
145514-04-1
http://www.bocsci.com/description.asp?cas=145514-04-1
Compound Cloud
124088
eMolecules
109867526
https://orderbb.emolecules.com/search/#?query=109867526
eMolecules
76746369
https://orderbb.emolecules.com/search/#?query=76746369
MuseChem
M091480
https://www.musechem.com/product/M091480.html
PubMed

PubMed

TitleDatePubMed
New trends in nucleoside biotechnology.
2010-07
Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome.
2010-04-01
Simultaneous quantification of intracellular natural and antiretroviral nucleosides and nucleotides by liquid chromatography-tandem mass spectrometry.
2010-03-01
Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals.
2010
Simultaneous quantification of 9-(beta-D-1,3-dioxolan-4-yl)guanine, Amdoxovir and Zidovudine in human plasma by liquid chromatography-tandem mass spectrometric assay.
2009-11-01
Gateways to clinical trials.
2007-12
The use of beta-D-2,6-diaminopurine dioxolane with or without mycophenolate mofetil in drug-resistant HIV infection.
2007-10-01
Synthesis and anti-HIV activity of (-)-beta-D-(2R,4R)-1,3-dioxolane-2,6-diamino purine (DAPD) (amdoxovir) and (-)-beta-D-(2R,4R)-1,3-dioxolane guanosine (DXG) prodrugs.
2007-09
Determination of 19 antiretroviral agents in pharmaceuticals or suspected products with two methods using high-performance liquid chromatography.
2007-05-01
Amdoxovir versus placebo with enfuvirtide plus optimized background therapy for HIV-1-infected subjects failing current therapy (AACTG A5118).
2006
Short-term safety and pharmacodynamics of amdoxovir in HIV-infected patients.
2005-10-14
New targets and new drugs in the treatment of HIV.
2005-07
Gateways to clinical trials.
2005-06
Emerging anti-HIV drugs.
2005-05
Mechanism of anti-human immunodeficiency virus activity of beta-D-6-cyclopropylamino-2',3'-didehydro-2',3'-dideoxyguanosine.
2005-05
Anabolism of amdoxovir: phosphorylation of dioxolane guanosine and its 5'-phosphates by mammalian phosphotransferases.
2004-11-01
In vitro combination of amdoxovir and the inosine monophosphate dehydrogenase inhibitors mycophenolic acid and ribavirin demonstrates potent activity against wild-type and drug-resistant variants of human immunodeficiency virus type 1.
2004-11
New nucleoside reverse transcriptase inhibitors for the treatment of HIV infections.
2004-10
HIV-chemotherapy and -prophylaxis: new drugs, leads and approaches.
2004-09
Favorable interactions between enfuvirtide and 1-beta-D-2,6-diaminopurine dioxolane in vitro.
2003-11
Effects of pyrimidine and purine analog combinations in the duck hepatitis B virus infection model.
2003-06
Dioxolane guanosine 5'-triphosphate, an alternative substrate inhibitor of wild-type and mutant HIV-1 reverse transcriptase. Steady state and pre-steady state kinetic analyses.
2003-05-23
[Antiretroviral therapy 2003. The current status].
2003-04-28
Gateways to clinical trials. March 2003.
2003-03
New antiretroviral drugs.
2003-03
In vitro activity of potential anti-poxvirus agents.
2003-01
Inhibitory activity of dioxolane purine analogs on wild-type and lamivudine-resistant mutants of hepadnaviruses.
2002-09
Highlights in the development of new antiviral agents.
2002-04
Novel use of a guanosine prodrug approach to convert 2',3'-didehydro-2',3'-dideoxyguanosine into a viable antiviral agent.
2002-03
Dioxolane guanosine, the active form of the prodrug diaminopurine dioxolane, is a potent inhibitor of drug-resistant HIV-1 isolates from patients for whom standard nucleoside therapy fails.
2002-01-01
In vitro susceptibilities of wild-type or drug-resistant hepatitis B virus to (-)-beta-D-2,6-diaminopurine dioxolane and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil.
2001-09
Mechanism of action of 1-beta-D-2,6-diaminopurine dioxolane, a prodrug of the human immunodeficiency virus type 1 inhibitor 1-beta-D-dioxolane guanosine.
2001-01
Ribavirin and mycophenolic acid potentiate the activity of guanine- and diaminopurine-based nucleoside analogues against hepatitis B virus.
2000-11
In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine.
2000-07
Mechanism of action and in vitro activity of 1',3'-dioxolanylpurine nucleoside analogues against sensitive and drug-resistant human immunodeficiency virus type 1 variants.
1999-10
Anti-HIV-1 activities of 1,3-dioxolane guanine and 2,6-diaminopurine dioxolane.
1999-08-05
Perspectives for the treatment of hepatitis B virus infections.
1999-07
1,3-dioxolanylpurine nucleosides (2R,4R) and (2R,4S) with selective anti-HIV-1 activity in human lymphocytes.
1993-01-08
Patents

Patents

EP1694363A2
1
US5444063
1
US5925643
1
US8609627
1
WO2011077100A1
1

Sample Use Guides

In Vivo Use Guide
300 mg twice daily
Route of Administration: Oral
In Vitro Use Guide
Amdoxovir proved equipotent at inhibiting HBV replication in HepG2 2.2.15, HepAD79 and HepAD38 cells with EC50 13, 16 and 14 ug/ml respectively.
Substance Class Chemical
Created
by admin
on Wed Apr 02 09:59:51 GMT 2025
Edited
by admin
on Wed Apr 02 09:59:51 GMT 2025
Record UNII
54I81H0M9C
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMDOXOVIR
INN   USAN  
USAN   INN  
Official Name English
DAPD
Preferred Name English
Amdoxovir [WHO-DD]
Common Name English
(-)-DAPD
Common Name English
amdoxovir [INN]
Common Name English
AMDOXOVIR [USAN]
Common Name English
1,3-DIOXOLANE-2-METHANOL, 4-(2,6-DIAMINO-9H-PURIN-9-YL)-, (2R,4R)-
Systematic Name English
(2R,4R)-4-(2,6-Diamino-9H-purin-9-yl)-1,3-dioxolane-2-methanol
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C97452
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
Code System Code Type Description
USAN
MM-19
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
FDA UNII
54I81H0M9C
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
ChEMBL
CHEMBL458876
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
EVMPD
SUB20547
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
INN
8124
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
MESH
C098393
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
SMS_ID
100000085765
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
CAS
145514-04-1
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
PUBCHEM
124088
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
NCI_THESAURUS
C76927
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
DRUG BANK
DB06619
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
EPA CompTox
DTXSID801027435
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
WIKIPEDIA
AMDOXOVIR
Created by admin on Wed Apr 02 09:59:51 GMT 2025 , Edited by admin on Wed Apr 02 09:59:51 GMT 2025
PRIMARY
Related Record Type Details
HUMAN IMMUNODEFICIENCY VIRUS TYPE 1
TARGET ORGANISM->INHIBITOR
Related Record Type Details
Structure of AMDOXOVIR
ACTIVE MOIETY
NIH
NCATS
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