4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one

• ChemBase编号: 590
• 分子式: C8H11N3O3S
• 平均质量: 229.25624
• 单一同位素质量: 229.05211223
• SMILES: S1C[C@H](O[C@H]1CO)n1ccc(nc1=O)N
• Canonical SMILES: Nc1ccn(c(=O)n1)[C@@H]1CS[C@@H](O1)CO
• InChI: InChI=1S/C8H11N3O3S/c9-5-1-2-11(8(13)10-5)6-4-15-7(3-12)14-6/h1-2,6-7,12H,3-4H2,(H2,9,10,13)/t6-,7+/m0/s1
• InChIKey: JTEGQNOMFQHVDC-NKWVEPMBSA-N

名称和登记号

名称

• IUPAC标准名: 4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one
• IUPAC传统名: lamivudine; 4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one
• 商标名: 3TC; Epivir; Epivir-HBV; Hepitec; Heptovir; Zeffix
• 别名: Lamivudine [Usan:Ban:Inn]; Lamivudine; 4-Amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone; (2R-cis)-4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone; (-)-2'-Deoxy-3'-thiacytidine; (-)-BCH 189; Epivir HBV; Hepitec; Heptodin; L-SddC; Lamivir; Virolam; β-L-2',3'-Dideoxy-3'-thiacytidine; β-L-3'-Thia-2',3'-dideoxycytidine; 4-amino-1-((2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl)pyrimidin-2(1H)-one; 2′,3′-Dideoxy-3′-thiacytidine; Lamivudine; 3TC; Zeffix; Heptovir; Epivir; Epivir-HBV

登记号

• CAS号: 134678-17-4
• MDL号: MFCD00869739
• PubChem SID: 160964053; 46507855
• PubChem CID: 60825

理论计算性质

JChem

• Acid pKa: 14.294604
• 质子受体: 5
• 质子供体: 2
• LogD (pH = 5.5): -1.0951098
• LogD (pH = 7.4): -1.0951077
• Log P: -1.0951076
• 摩尔折射率: 55.1645 cm^3
• 极化性: 21.351086 Å^3
• 极化表面积: 88.15 Å^2
• 可自由旋转的化学键: 2
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: -1.29
• LOG S: -1.92
• 溶解度: 2.76e+00 g/l

分子性质

理化性质

• 溶解度: 70 mg/ml; DMSO: >20 mg/mL; Methanol; Sparingly Sol. in Ethanol; Water
• 外观: White Solid; white to off-white powder
• 熔点: 171-173°C
• 疏水性(logP): -1.4

安全信息

• 保存条件: -20°C; Refrigerator
• 欧盟危险性物质标志: 刺激性(Irritant) (Xi)
• 德国WGK号: 3
• 危险公开号: 36/37/38
• 安全公开号: 26-36
• GHS危险品标识: GHS07
• GHS警示词: Warning
• GHS危险声明: H315-H319-H335
• GHS警示性声明: P261-P305 + P351 + P338
• 保存温度: room temp

药理学性质

• 生物活性机理: HIV reverse transcriptase inhibitor

产品相关信息

• 纯度: ≥98% (HPLC); 95+%
• 成盐信息: Free Base
• 应用领域: Active against hepatitis B virus and human immunodeficiency virus; Potent antiviral agent
• Empirical Formula (Hill Notation): C8H11N3O3S

详细说明

DrugBank - DB00709

• Drug Groups: approved; investigational
• Description: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat Human Immunodeficiency Virus Type 1 (HIV-1) and hepatitis B (HBV).
• Indication: For the treatment of HIV infection and chronic hepatitis B (HBV).
• Pharmacology: Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1) and hepatitis B (HBV). Lamivudine 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.
• Affected Organisms: Human Immunodeficiency Virus; Hepatitis B virus
• Biotransformation: The only detected metabolite of lamivudine is trans-sulfoxide.
• Absorption: Lamivudine was rapidly absorbed after oral administration in HIV-infected patients. Absolute bioavailability in adults is 86% ± 16% for the tablet and 87% ± 13% for the oral solution.
• Half Life: 5 to 7 hours
• Protein Binding: 36%
• Elimination: The primary routes of elimination of abacavir are metabolism by alcohol dehydrogenase to form the 5′-carboxylic acid and glucuronyl transferase to form the 5′-glucuronide. Lamivudine is excreted in human breast milk and into the milk of lactating rats.
• Clearance: * Renal cl=280.4?+/-?75.2 mL/min [HIV-infected?patients given a single IV doses ranging from 0.25 to 8 mg/kg]
• References: Fox Z, Dragsted UB, Gerstoft J, Phillips AN, Kjaer J, Mathiesen L, Youle M, Katlama C, Hill A, Bruun JN, Clumeck N, Dellamonica P, Lundgren JD: A randomized trial to evaluate continuation versus discontinuation of lamivudine in individuals failing a lamivudine-containing regimen: the COLATE trial. Antivir Ther. 2006;11(6):761-70. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1706

Research Area: Infection
Biological Activity:
Lamivudine(Epivir) is a potent nucleoside analog reverse transcriptase inhibitor with an IC50 of 2.7 mM. [1] The pH-driven uptake of TEA by BBMV (pHin = 6.0, pHout = 7.5) was inhibited by lamivudine. The IC50 value (concentration resulting in 50% inhibition) for the concentration-dependent effect of lamivudine on TEA uptake by BBMV after 30 s was 2668 µM whereas IC50 values for cimetidine and trimethoprim were < 2.5 µM and < 25 µM, respectively. The early uptake of TEA by BLMV was also reduced significantly by lamivudine. The IC50 value for the concentration-dependent effect of lamivudine on uptake of TEA by BLMV at 30 s was > 25 mM, whereas the IC50 values for cimetidine and trimethoprim were 2116 µM and 445µM, respectively. [2]

Sigma Aldrich - L1295

Biochem/physiol Actions
Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor (nRTI). It is an analogue of cytidine, and can inhibit both types (1 and 2) of HIV reverse transcriptase as well as the reverse transcriptase of hepatitis B. It needs to be phosphorylated to its triphosphate form before it is active. 3TC-triphosphate also inhibits cellular DNA polymerase.

Toronto Research Chemicals - L172500

Lamivudine is a potent nucleoside reverse transcriptase inhibitor. Antiviral. Lamivudine has been used for treatment of chronic hepatitis B.

参考文献

• Fox Z, Dragsted UB, Gerstoft J, Phillips AN, Kjaer J, Mathiesen L, Youle M, Katlama C, Hill A, Bruun JN, Clumeck N, Dellamonica P, Lundgren JD: A randomized trial to evaluate continuation versus discontinuation of lamivudine in individuals failing a lamivudine-containing regimen: the COLATE trial. Antivir Ther. 2006;11(6):761-70. Pubmed
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