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Details

Stereochemistry ABSOLUTE
Molecular Formula C9H12N6O3
Molecular Weight 252.2303
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMDOXOVIR

SMILES

C([C@]1([H])OC[C@]([H])(n2cnc3c(N)[nH]c(=N)nc32)O1)O

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 252.2303
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
499 ng/mL
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
1545 ng/mL
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
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1326 ng × h/mL
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
6834 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.4 h
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
17.6 h
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
Doses

Doses

DosePopulationAdverse events​
500 mg 2 times / day multiple, oral (unknown)
Highest studied dose
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
unhealthy
n = 8
Health Status: unhealthy
Condition: HIV infection
Sex: M
Population Size: 8
Sources:
PubMed

PubMed

TitleDatePubMed
1,3-dioxolanylpurine nucleosides (2R,4R) and (2R,4S) with selective anti-HIV-1 activity in human lymphocytes.
1993 Jan 8
Anti-HIV-1 activities of 1,3-dioxolane guanine and 2,6-diaminopurine dioxolane.
1999 Apr-May
Perspectives for the treatment of hepatitis B virus infections.
1999 Jul
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 Oct
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 Jul
Ribavirin and mycophenolic acid potentiate the activity of guanine- and diaminopurine-based nucleoside analogues against hepatitis B virus.
2000 Nov
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 Jan
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 Sep
Highlights in the development of new antiviral agents.
2002 Apr
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 Jan 1
Novel use of a guanosine prodrug approach to convert 2',3'-didehydro-2',3'-dideoxyguanosine into a viable antiviral agent.
2002 Mar
Inhibitory activity of dioxolane purine analogs on wild-type and lamivudine-resistant mutants of hepadnaviruses.
2002 Sep
[Antiretroviral therapy 2003. The current status].
2003 Apr 28
In vitro activity of potential anti-poxvirus agents.
2003 Jan
Effects of pyrimidine and purine analog combinations in the duck hepatitis B virus infection model.
2003 Jun
Gateways to clinical trials. March 2003.
2003 Mar
New antiretroviral drugs.
2003 Mar
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 May 23
Favorable interactions between enfuvirtide and 1-beta-D-2,6-diaminopurine dioxolane in vitro.
2003 Nov
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 Nov
Anabolism of amdoxovir: phosphorylation of dioxolane guanosine and its 5'-phosphates by mammalian phosphotransferases.
2004 Nov 1
New nucleoside reverse transcriptase inhibitors for the treatment of HIV infections.
2004 Oct
HIV-chemotherapy and -prophylaxis: new drugs, leads and approaches.
2004 Sep
New targets and new drugs in the treatment of HIV.
2005 Jul
Gateways to clinical trials.
2005 Jun
Emerging anti-HIV drugs.
2005 May
Mechanism of anti-human immunodeficiency virus activity of beta-D-6-cyclopropylamino-2',3'-didehydro-2',3'-dideoxyguanosine.
2005 May
Short-term safety and pharmacodynamics of amdoxovir in HIV-infected patients.
2005 Oct 14
Amdoxovir versus placebo with enfuvirtide plus optimized background therapy for HIV-1-infected subjects failing current therapy (AACTG A5118).
2006
Gateways to clinical trials.
2007 Dec
Determination of 19 antiretroviral agents in pharmaceuticals or suspected products with two methods using high-performance liquid chromatography.
2007 May 1
The use of beta-D-2,6-diaminopurine dioxolane with or without mycophenolate mofetil in drug-resistant HIV infection.
2007 Oct 1
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 Sep
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 Nov 1
Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals.
2010
Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome.
2010 Apr 1
New trends in nucleoside biotechnology.
2010 Jul
Simultaneous quantification of intracellular natural and antiretroviral nucleosides and nucleotides by liquid chromatography-tandem mass spectrometry.
2010 Mar 1
Patents

Sample Use Guides

300 mg twice daily
Route of Administration: Oral
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 Sat Jun 26 04:05:14 UTC 2021
Edited
by admin
on Sat Jun 26 04:05:14 UTC 2021
Record UNII
54I81H0M9C
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMDOXOVIR
INN   USAN  
USAN   INN  
Official Name English
(-)-DAPD
Common Name English
AMDOXOVIR [INN]
Common Name English
DAPD
Code 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 Sat Jun 26 04:05:14 UTC 2021 , Edited by admin on Sat Jun 26 04:05:14 UTC 2021
Code System Code Type Description
FDA UNII
54I81H0M9C
Created by admin on Sat Jun 26 04:05:14 UTC 2021 , Edited by admin on Sat Jun 26 04:05:14 UTC 2021
PRIMARY
ChEMBL
CHEMBL458876
Created by admin on Sat Jun 26 04:05:14 UTC 2021 , Edited by admin on Sat Jun 26 04:05:14 UTC 2021
PRIMARY
EVMPD
SUB20547
Created by admin on Sat Jun 26 04:05:14 UTC 2021 , Edited by admin on Sat Jun 26 04:05:14 UTC 2021
PRIMARY
INN
8124
Created by admin on Sat Jun 26 04:05:14 UTC 2021 , Edited by admin on Sat Jun 26 04:05:14 UTC 2021
PRIMARY
MESH
C098393
Created by admin on Sat Jun 26 04:05:14 UTC 2021 , Edited by admin on Sat Jun 26 04:05:14 UTC 2021
PRIMARY
CAS
145514-04-1
Created by admin on Sat Jun 26 04:05:14 UTC 2021 , Edited by admin on Sat Jun 26 04:05:14 UTC 2021
PRIMARY
PUBCHEM
124088
Created by admin on Sat Jun 26 04:05:14 UTC 2021 , Edited by admin on Sat Jun 26 04:05:14 UTC 2021
PRIMARY
NCI_THESAURUS
C76927
Created by admin on Sat Jun 26 04:05:14 UTC 2021 , Edited by admin on Sat Jun 26 04:05:14 UTC 2021
PRIMARY
DRUG BANK
DB06619
Created by admin on Sat Jun 26 04:05:14 UTC 2021 , Edited by admin on Sat Jun 26 04:05:14 UTC 2021
PRIMARY
WIKIPEDIA
AMDOXOVIR
Created by admin on Sat Jun 26 04:05:14 UTC 2021 , Edited by admin on Sat Jun 26 04:05:14 UTC 2021
PRIMARY
Related Record Type Details
TARGET ORGANISM->INHIBITOR
Related Record Type Details
ACTIVE MOIETY