CAS 30516-87-1|zidovudine|Zidovudine|Retrovir|Zidovudine EP III|Apo-Zidovudine|Azidothymidine|1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione|Azte...

General Information

Structure

Molecular Formula

C₁₀H₁₃N₅O₄

Molecular Mass

267.24132

Exact Mass

267.09675392

Charge

InChI

InChI=1S/C10H13N5O4/c1-5-3-15(10(18)12-9(5)17)8-2-6(13-14-11)7(4-16)19-8/h3,6-8,16H,2,4H2,1H3,(H,12,17,18)/t6-,7+,8+/m0/s1

InChIKey

HBOMLICNUCNMMY-XLPZGREQSA-N

Canonic Smiles

OC[C@H]1O[C@H](C[C@@H]1N=[N+]=[N-])n1cc(C)c(=O)[nH]c1=O

Isomeric Smiles

O1[C@@H](n2cc(c(=O)[nH]c2=O)C)C[C@H](N=[N+]=[N-])[C@H]1CO

Calculated Properties

JChem

LogD (pH = 7.4)

-0.41

LogD (pH = 5.5)

-0.41

Log P

-0.30

Rotatable Bonds

H Donor

H Acceptors

Lipinski's Rule of Five

true

Acid pKa

9.96

Polar Surface Area

108.30

Polarizability

24.81

Molar Refractivity

61.70

LOG S

-1.23

Data Source

Names and Identifiers

IUPAC Traditional name

zidovudine

Synonyms

Zidovudineazidothymidine3′-叠氮-3′-脱氧胸苷叠氮胸苷ZidovudineRetrovir齐多夫定3′-Azido-3′-deoxythymidineZDVAZTzidovudineAzidothymidineZidovudinZidovudinumAZT

Brand Name

RetrovirZidovudine EP IIIApo-ZidovudineAzidothymidineAztecNovo-AztCompound S

IUPAC name

1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione

API Name

Zidovudine

International Nonproprietary Name (INN)

zidovudine

Names and Identifiers

Registration numbers

Properties

Physical Property

Solubility

10-50 g/L at 17 oC

H2O: soluble50 mg/mL, clear, colorless to slightly yellow

Hydrophobicity(logP)

0.05

Melting Point

113-115 °C(lit.)

Optical Rotation

[α]20/D +47°, c = 0.5 in H2O

Product Information

Properties

Related Proteins

Molecular Spectra

No Data Available

Click here to submit data

Molecule Details

DrugBank

DB00495

Drug Groups

approved

Description

A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [PubChem]

Indication

For the treatment of human immunovirus (HIV) infections.

Pharmacology

Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Zidovudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.

Toxicity

Symptoms of overdose include fatigue, headache, nausea, and vomiting. LD₅₀ is 3084 mg/kg (orally in mice).

Affected Organisms

Human Immunodeficiency Virus

Biotransformation

Hepatic. Metabolized by glucuronide conjugation to major, inactive metabolite, 3′-azido-3′-deoxy-5′- O-beta-D-glucopyranuronosylthymidine (GZDV).

Absorption

Rapid and nearly complete absorption from the gastrointestinal tract following oral administration; however, because of first-pass metabolism, systemic bioavailability of zidovudine capsules and solution is approximately 65% (range, 52 to 75%). Bioavailability in neonates up to 14 days of age is approximately 89%, and it decreases to approximately 61% and 65% in neonates over 14 days of age and children 3 months to 12 years, respectively. Administration with a high-fat meal may decrease the rate and extent of absorption.

Half Life

0.5-3 hours

Protein Binding

30-38%

Elimination

As in adult patients, the major route of elimination was by metabolism to GZDV. After intravenous dosing, about 29% of the dose was excreted in the urine unchanged and about 45% of the dose was excreted as GZDV

Clearance

* 0.65?+/- 0.29 L/hr/kg [HIV-infected, Birth to 14?Days of Age]
* 1.14?+/- 0.24 L/hr/kg [HIV-infected, 14?Days to 3 Months of Age]
* 1.85 +/- 0.47 L/hr/kg [HIV-infected, 3 Months to 12?Years of Age]

References

• De Clercq E: HIV resistance to reverse transcriptase inhibitors. Biochem Pharmacol. 1994 Jan 20;47(2):155-69. [Pubmed]

• Yarchoan R, Mitsuya H, Broder S: AIDS therapies. Sci Am. 1988 Oct;259(4):110-9. [Pubmed]

• Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, VanDyke R, Bey M, Shearer W, Jacobson RL, et al.: Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994 Nov 3;331(18):1173-80. [Pubmed]

• Mitsuya H, Yarchoan R, Broder S: Molecular targets for AIDS therapy. Science. 1990 Sep 28;249(4976):1533-44. [Pubmed]

• Mitsuya H, Weinhold KJ, Furman PA, St Clair MH, Lehrman SN, Gallo RC, Bolognesi D, Barry DW, Broder S: 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7096-100. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [PDRhealth]

• [Drugs.com]

Selleck Chemicals

S2579

Research Area: Infection
Biological Activity:
Zidovudine (Retrovir) is a reverse transcriptase inhibitor. Zidovudine (Retrovir) is a nucleoside analog reverse transcriptase inhibitor (NRTI), a type of antiretroviral drug used for the treatment of HIV/AIDS. Zidovudine (Retrovir) is an analog of thymidine.Like other reverse transcriptase inhibitors, Zidovudine (Retrovir) works by inhibiting the action of reverse transcriptase, the enzyme that HIV uses to make a DNA copy of its RNA. Reverse transcription is necessary for production of the viral double-stranded DNA, which is subsequently integrated into the genetic material of the infected cell. The triphosphate form also inhibits DNA polymerase used by human cells to undergo cell division, but has approximately 100-fold greater affinity for viral reverse transcriptase. [1][2][3]References on Zidovudine (Retrovir)[1] http://en.wikipedia.org/wiki/Zidovudine, , [2] Science., 1990 Sep 28, 249(4976):1533-44[3] Proc Natl Acad Sci U S A., 1986 Nov, 83(21):8333-7

Sigma Aldrich

323608

Biochem/physiol Actions
Reverse transcriptase inhibitor active against HIV-1 virus.

11546

Biochem/physiol Actions
Reverse transcriptase inhibitor active against HIV-1 virus.
Other Notes
A potent, selective inhibitor of human immunodeficiency virus replication in MT-4 and ATH8 cells1

ChEBI

CHEBI:10110

A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase.

Molecule Details

References

PubChem Literature

From Data Sources

• Mitsuya H, Yarchoan R, Broder S: Molecular targets for AIDS therapy. Science. 1990 Sep 28;249(4976):1533-44. Pubmed

• De Clercq E: HIV resistance to reverse transcriptase inhibitors. Biochem Pharmacol. 1994 Jan 20;47(2):155-69. Pubmed

• Yarchoan R, Mitsuya H, Broder S: AIDS therapies. Sci Am. 1988 Oct;259(4):110-9. Pubmed

• Mitsuya H et al. Science. 1990 Sep 28;249(4976):1533-44.

References

Bioactivity

PubChem BioAssay

Bioactivity

Names and Identifiers

IUPAC Traditional name

zidovudine

Synonyms

Zidovudineazidothymidine3′-叠氮-3′-脱氧胸苷叠氮胸苷ZidovudineRetrovir齐多夫定3′-Azido-3′-deoxythymidineZDVAZTzidovudineAzidothymidineZidovudinZidovudinumAZT

Brand Name

RetrovirZidovudine EP IIIApo-ZidovudineAzidothymidineAztecNovo-AztCompound S

IUPAC name

1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione

API Name

Zidovudine

International Nonproprietary Name (INN)

zidovudine

Properties

Physical Property

Solubility

10-50 g/L at 17 oC

H2O: soluble50 mg/mL, clear, colorless to slightly yellow

Hydrophobicity(logP)

0.05

Melting Point

113-115 °C(lit.)

Optical Rotation

[α]20/D +47°, c = 0.5 in H2O

Product Information

Molecule Details

DrugBank

DB00495

Drug Groups

approved

Description

Indication

For the treatment of human immunovirus (HIV) infections.

Pharmacology

Toxicity

Symptoms of overdose include fatigue, headache, nausea, and vomiting. LD₅₀ is 3084 mg/kg (orally in mice).

Affected Organisms

Human Immunodeficiency Virus

Biotransformation

Hepatic. Metabolized by glucuronide conjugation to major, inactive metabolite, 3′-azido-3′-deoxy-5′- O-beta-D-glucopyranuronosylthymidine (GZDV).

Absorption

Half Life

0.5-3 hours

Protein Binding

30-38%

Elimination

Clearance

* 0.65?+/- 0.29 L/hr/kg [HIV-infected, Birth to 14?Days of Age]
* 1.14?+/- 0.24 L/hr/kg [HIV-infected, 14?Days to 3 Months of Age]
* 1.85 +/- 0.47 L/hr/kg [HIV-infected, 3 Months to 12?Years of Age]

References

• De Clercq E: HIV resistance to reverse transcriptase inhibitors. Biochem Pharmacol. 1994 Jan 20;47(2):155-69. [Pubmed]

• Yarchoan R, Mitsuya H, Broder S: AIDS therapies. Sci Am. 1988 Oct;259(4):110-9. [Pubmed]

• Mitsuya H, Yarchoan R, Broder S: Molecular targets for AIDS therapy. Science. 1990 Sep 28;249(4976):1533-44. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [PDRhealth]

• [Drugs.com]

Selleck Chemicals

S2579

Sigma Aldrich

323608

Biochem/physiol Actions
Reverse transcriptase inhibitor active against HIV-1 virus.

11546

Biochem/physiol Actions
Reverse transcriptase inhibitor active against HIV-1 virus.
Other Notes
A potent, selective inhibitor of human immunodeficiency virus replication in MT-4 and ATH8 cells1

ChEBI

CHEBI:10110

A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase.

References

PubChem Literature

From Data Sources

• Mitsuya H, Yarchoan R, Broder S: Molecular targets for AIDS therapy. Science. 1990 Sep 28;249(4976):1533-44. Pubmed

• De Clercq E: HIV resistance to reverse transcriptase inhibitors. Biochem Pharmacol. 1994 Jan 20;47(2):155-69. Pubmed

• Yarchoan R, Mitsuya H, Broder S: AIDS therapies. Sci Am. 1988 Oct;259(4):110-9. Pubmed

• Mitsuya H et al. Science. 1990 Sep 28;249(4976):1533-44.

Bioactivity

PubChem BioAssay

Molecule

ID:378