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

• ChemBase编号: 378
• 分子式: C10H13N5O4
• 平均质量: 267.24132
• 单一同位素质量: 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

名称和登记号

名称

• 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
• IUPAC传统名: zidovudine
• 商标名: Apo-Zidovudine; Azidothymidine; Aztec; Compound S; Novo-Azt; Retrovir; Zidovudine EP III
• 别名: 叠氮胸苷; 齐多夫定; 3′-叠氮-3′-脱氧胸苷; Zidovudine; azidothymidine; Retrovir; AZT; ZDV; Zidovudine; 3′-Azido-3′-deoxythymidine

登记号

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

理论计算性质

JChem

• Acid pKa: 9.960416
• 质子受体: 6
• 质子供体: 2
• LogD (pH = 5.5): -0.41276968
• LogD (pH = 7.4): -0.41393453
• Log P: -0.29870915
• 摩尔折射率: 61.7045 cm^3
• 极化性: 23.694994 Å^3
• 极化表面积: 108.3 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: -0.1
• LOG S: -1.21
• 溶解度: 1.63e+01 g/l

分子性质

理化性质

• 溶解度: 10-50 g/L at 17 oC; H2O: soluble50 mg/mL, clear, colorless to slightly yellow
• 熔点: 113-115 °C(lit.)
• 比旋光度: [α]20/D +47°, c = 0.5 in H2O
• 疏水性(logP): 0.05

安全信息

• 保存条件: -20°C
• RTECS编号: XP2072000
• 欧盟危险性物质标志: 有害性(Harmful) (Xn)
• 德国WGK号: 3
• 危险公开号: 40
• 安全公开号: 36/37/39-45
• GHS危险品标识: GHS08
• GHS警示词: Warning
• GHS危险声明: H351
• GHS警示性声明: P281
• 个人保护装置: 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
• 保存温度: -20°C

产品相关信息

• 纯度: ≥99.0% (HPLC); 98%
• 成盐信息: Free Base
• 杂质: ≤0.5% water
• Empirical Formula (Hill Notation): C10H13N5O4

详细说明

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• Description: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group.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。

Sigma Aldrich - 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

参考文献

• 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.