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

基本信息

化学结构

分子式

C₁₀H₁₃N₅O₄

分子量

267.24132

精确质量

267.09675392

电荷

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

计算属性

JChem

LogD (pH = 7.4)

-0.41

LogD (pH = 5.5)

-0.41

Log P

-0.30

可自由旋转的化学键

质子供体

质子受体

里宾斯基五规则

true

Acid pKa

9.96

极化表面积

108.30

极化性

24.81

摩尔折射率

61.70

LOG S

-1.23

数据来源

名称和标识

IUPAC传统名

zidovudine

别名

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

商标名

RetrovirZidovudine EP IIIApo-ZidovudineAzidothymidineAztecNovo-AztCompound S

IUPAC标准名

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

API名称

Zidovudine

国际非专利药品(INN)

zidovudine

名称和标识

数据登录号

化合物性质

理化性质

溶解度

10-50 g/L at 17 oC

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

疏水性(logP)

0.05

熔点

113-115 °C(lit.)

比旋光度

[α]20/D +47°, c = 0.5 in H2O

产品相关信息

化合物性质

分子相关蛋白质

分子图谱

暂无数据

点击上传数据

描述信息

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A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group.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
对 HIV-1 病毒有效的逆转录酶抑制剂。

11546

Biochem/physiol Actions
对 HIV-1 病毒有效的逆转录酶抑制剂。
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.

描述信息

参考文献

PubChem文献

数据源提供

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

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

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

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

参考文献

生物活性

PubChem BioAssay

生物活性

名称和标识

IUPAC传统名

zidovudine

别名

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

商标名

RetrovirZidovudine EP IIIApo-ZidovudineAzidothymidineAztecNovo-AztCompound S

IUPAC标准名

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

API名称

Zidovudine

国际非专利药品(INN)

zidovudine

描述信息

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
对 HIV-1 病毒有效的逆转录酶抑制剂。

11546

Biochem/physiol Actions
对 HIV-1 病毒有效的逆转录酶抑制剂。
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.

参考文献

PubChem文献

数据源提供

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

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

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

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

生物活性

PubChem BioAssay

化合物性质

理化性质

溶解度

10-50 g/L at 17 oC

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

疏水性(logP)

0.05

熔点

113-115 °C(lit.)

比旋光度

[α]20/D +47°, c = 0.5 in H2O

产品相关信息

化合物信息

ID:378