AMDOXOVIR

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 Search

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15351346
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

Targets

Primary Target	Pharmacology	Potency
DNA polymerase/reverse transcriptase 10 Target ID: CHEMBL2362994 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10760047	Inhibitor 8297	0.61 µM [IC50]
Adenosine deaminase 13 Target ID: CHEMBL2966 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120959	Substrate 661
Human immunodeficiency virus type 1 reverse transcriptase 67 Target ID: CHEMBL247 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120959 \| http://adisinsight.springer.com/drugs/800004771	Inhibitor 8297	0.019 µM [Ki]
DNA polymerase beta 5 Target ID: CHEMBL2392 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120959	Inhibitor 8297	32.0 µM [Ki]
DNA polymerase alpha subunit 9 Target ID: CHEMBL1828 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120959	Inhibitor 8297	78.0 µM [Ki]
DNA polymerase gamma subunit 1 2 Target ID: CHEMBL2732 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120959	Inhibitor 8297	4.3 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 151 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16964830	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
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
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

AUC

Value	Dose	Co-administered	Analyte	Population
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
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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
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

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/16184030	unhealthy n = 8 Health Status: unhealthy Condition: HIV infection Sex: M Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/16184030	Sources: https://pubmed.ncbi.nlm.nih.gov/16184030

Sourcing

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

PubMed

Title	Date	PubMed
1,3-dioxolanylpurine nucleosides (2R,4R) and (2R,4S) with selective anti-HIV-1 activity in human lymphocytes.	1993 Jan 8	8421287
Ribavirin and mycophenolic acid potentiate the activity of guanine- and diaminopurine-based nucleoside analogues against hepatitis B virus.	2000 Nov	11114413
[Antiretroviral therapy 2003. The current status].	2003 Apr 28	15011574
Effects of pyrimidine and purine analog combinations in the duck hepatitis B virus infection model.	2003 Jun	12760857
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	12651859
Favorable interactions between enfuvirtide and 1-beta-D-2,6-diaminopurine dioxolane in vitro.	2003 Nov	14576137
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	15504868
Anabolism of amdoxovir: phosphorylation of dioxolane guanosine and its 5'-phosphates by mammalian phosphotransferases.	2004 Nov 1	15450953
New nucleoside reverse transcriptase inhibitors for the treatment of HIV infections.	2004 Oct	15351346
HIV-chemotherapy and -prophylaxis: new drugs, leads and approaches.	2004 Sep	15183346
New targets and new drugs in the treatment of HIV.	2005 Jul	16373002
Gateways to clinical trials.	2005 Jun	16082422
Emerging anti-HIV drugs.	2005 May	15934866
Mechanism of anti-human immunodeficiency virus activity of beta-D-6-cyclopropylamino-2',3'-didehydro-2',3'-dideoxyguanosine.	2005 May	15855524
Short-term safety and pharmacodynamics of amdoxovir in HIV-infected patients.	2005 Oct 14	16184030
Amdoxovir versus placebo with enfuvirtide plus optimized background therapy for HIV-1-infected subjects failing current therapy (AACTG A5118).	2006	16964830
Gateways to clinical trials.	2007 Dec	18200333
Determination of 19 antiretroviral agents in pharmaceuticals or suspected products with two methods using high-performance liquid chromatography.	2007 May 1	17196448
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	17532483
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	19740712
Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome.	2010 Apr 1	20376347
New trends in nucleoside biotechnology.	2010 Jul	22649640

Patents

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 `Sat Dec 16 18:04:04 GMT 2023` Edited by `admin` on `Sat Dec 16 18:04:04 GMT 2023`
Record UNII	54I81H0M9C
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMDOXOVIR

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