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

• ChemBase ID: 590
• Molecular Formular: C8H11N3O3S
• Molecular Mass: 229.25624
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one
• IUPAC Traditional name: lamivudine; 4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one
• Brand Name: 3TC; Epivir; Epivir-HBV; Hepitec; Heptovir; Zeffix
• Synonyms: 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

Database IDs

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

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.294604
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): -1.0951098
• LogD (pH = 7.4): -1.0951077
• Log P: -1.0951076
• Molar Refractivity: 55.1645 cm^3
• Polarizability: 21.351086 Å^3
• Polar Surface Area: 88.15 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -1.29
• LOG S: -1.92
• Solubility (Water): 2.76e+00 g/l

PROPERTIES

Physical Property

• Solubility: 70 mg/ml; DMSO: >20 mg/mL; Methanol; Sparingly Sol. in Ethanol; Water
• Apperance: White Solid; white to off-white powder
• Melting Point: 171-173°C
• Hydrophobicity(logP): -1.4

Safety Information

• Storage Condition: -20°C; Refrigerator
• European Hazard Symbols: Irritant (Xi)
• German water hazard class: 3
• Risk Statements: 36/37/38
• Safety Statements: 26-36
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H315-H319-H335
• GHS Precautionary statements: P261-P305 + P351 + P338
• Storage Temperature: room temp

Pharmacology Properties

• Mechanism of Action: HIV reverse transcriptase inhibitor

Product Information

• Purity: ≥98% (HPLC); 95+%
• Salt Data: Free Base
• Application(s): Active against hepatitis B virus and human immunodeficiency virus; Potent antiviral agent
• Empirical Formula (Hill Notation): C8H11N3O3S

DETAILS

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.

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
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