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

• ChemBase ID: 378
• Molecular Formular: C10H13N5O4
• Molecular Mass: 267.24132
• Monoisotopic Mass: 267.09675392
• SMILES: O1[C@@H](n2cc(c(=O)[nH]c2=O)C)C[C@H](N=[N+]=[N-])[C@H]1CO
• Canonical SMILES: OC[C@H]1O[C@H](C[C@@H]1N=[N+]=[N-])n1cc(C)c(=O)[nH]c1=O
• 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

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
• IUPAC Traditional name: zidovudine
• Brand Name: Apo-Zidovudine; Azidothymidine; Aztec; Compound S; Novo-Azt; Retrovir; Zidovudine EP III
• Synonyms: Zidovudine; azidothymidine; Retrovir; AZT; ZDV; Zidovudine; 3′-Azido-3′-deoxythymidine; 叠氮胸苷; 齐多夫定; 3′-叠氮-3′-脱氧胸苷

Database IDs

• CAS Number: 30516-87-1
• MDL Number: MFCD00006536
• Beilstein Number: 3595791
• PubChem SID: 46508240; 160963841
• PubChem CID: 35370

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.960416
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): -0.41276968
• LogD (pH = 7.4): -0.41393453
• Log P: -0.29870915
• Molar Refractivity: 61.7045 cm^3
• Polarizability: 23.694994 Å^3
• Polar Surface Area: 108.3 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -0.1
• LOG S: -1.21
• Solubility (Water): 1.63e+01 g/l

PROPERTIES

Physical Property

• Solubility: 10-50 g/L at 17 oC; H2O: soluble50 mg/mL, clear, colorless to slightly yellow
• Melting Point: 113-115 °C(lit.)
• Optical Rotation: [α]20/D +47°, c = 0.5 in H2O
• Hydrophobicity(logP): 0.05

Safety Information

• Storage Condition: -20°C
• RTECS: XP2072000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 40
• Safety Statements: 36/37/39-45
• GHS Pictograms: GHS08
• GHS Signal Word: Warning
• GHS Hazard statements: H351
• GHS Precautionary statements: P281
• Personal Protective Equipment: Eyeshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• Storage Temperature: -20°C

Product Information

• Purity: ≥99.0% (HPLC); 98%
• Salt Data: Free Base
• Impurities: ≤0.5% water
• Empirical Formula (Hill Notation): C10H13N5O4

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.

Sigma Aldrich - 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

REFERENCES

• 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
• 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.