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

• ChemBase ID: 1133
• Molecular Formular: C10H14N2O5
• Molecular Mass: 242.22856
• Monoisotopic Mass: 242.09027156
• SMILES: O1[C@H](n2cc(c(=O)[nH]c2=O)C)C[C@@H](O)[C@@H]1CO
• Canonical SMILES: OC[C@@H]1O[C@@H](C[C@H]1O)n1cc(C)c(=O)[nH]c1=O
• InChI: InChI=1S/C10H14N2O5/c1-5-3-12(10(16)11-9(5)15)8-2-6(14)7(4-13)17-8/h3,6-8,13-14H,2,4H2,1H3,(H,11,15,16)/t6-,7+,8+/m1/s1
• InChIKey: IQFYYKKMVGJFEH-CSMHCCOUSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-[(2S,4R,5S)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
• IUPAC Traditional name: telbivudine
• Brand Name: Tyzeka; Sebivo
• Synonyms: 2'-Deoxy-L-thymidine; Beta-l-thymidine; Epavudine; L-DT; LDT; Telbivudin; L-deoxythymidine; L-thymidine; telbivudine; Telbivudine; 1-(2-Deoxy-beta-D-ribofuranosyl)-5-methyluracil; Thymidine; Tyzeka; Sebivo; L-ThyMidine

Database IDs

• CAS Number: 3424-98-4; 50-89-5
• MDL Number: MFCD00006537
• PubChem SID: 46508706; 160964596
• PubChem CID: 159269

CALCULATED PROPERTIES

JChem

• Acid pKa: 8.960321
• H Acceptors: 5
• H Donor: 3
• LogD (pH = 5.5): -1.1192024
• LogD (pH = 7.4): -1.1307083
• Log P: -1.1190536
• Molar Refractivity: 55.412 cm^3
• Polarizability: 22.001661 Å^3
• Polar Surface Area: 99.1 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -1.32
• LOG S: -0.56
• Solubility (Water): 6.68e+01 g/l

PROPERTIES

Physical Property

• Solubility: Sparingly soluble in water (>20 mg/mL)
• Melting Point: 186-188°C
• Hydrophobicity(logP): -1.4

Safety Information

• Storage Condition: -20°C

Product Information

• Purity: 97%
• Salt Data: Free Base

DETAILS

DrugBank - DB01265

• Drug Groups: approved; investigational
• Description: Telbivudine is a synthetic thymidine nucleoside analog with specific activity against the hepatitis B virus. Telbivudine is orally administered, with good tolerance, lack of toxicity and no dose-limiting side effects.
• Indication: For the treatment of chronic hepatitis B in adult and adolescent patients ≥16 years of age with evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
• Pharmacology: Telbivudine is a synthetic thymidine nucleoside analogue with activity against hepatitis B virus (HBV). Telbivudine is the unmodified β–L enantiomer of the naturally occurring nucleoside, thymidine. It undergoes phosphorylation via interaction with cellular kinases to form the active metabolite, telbivudine 5'-triphosphate.
• Toxicity: There is no information on intentional overdose of telbivudine, but one subject experienced an unintentional and asymptomatic overdose. Healthy subjects who received telbivudine doses up to 1800 mg/day for 4 days had no increase in or unexpected adverse events. A maximum tolerated dose for telbivudine has not been determined.
• Affected Organisms: Hepatitis B virus
• Biotransformation: No metabolites of telbivudine were detected following administration of [14C]–telbivudine in humans. Telbivudine is not a substrate, or inhibitor of the cytochrome P450 (CYP450) enzyme system.
• Absorption: Absorbed following oral administration. Telbivudine absorption and exposure were unaffected when a single 600–mg dose was administered with a high–fat (~55 g), high–calorie (~950 kcal) meal.
• Half Life: Approximately 15 hours.
• Protein Binding: In vitro binding of telbivudine to human plasma proteins is low (3.3%).
• Elimination: Telbivudine is eliminated primarily by urinary excretion of unchanged drug.
• Clearance: * 7.6 +/- 2.9 L/h [Normal renal function (Clcr>80 mL/min)]; * 5.0 +/- 1.2 L/h [Mild renal function impairement (Clcr=50-80 mL/min)]; * 2.6 +/- 1.2 L/h [Moderate renal function impairement (Clcr=30-49 mL/min)]; * 0.7 +/- 0.4 L/h [Severe renal function impairement (Clcr<30 mL/min)]
• References: Matthews SJ: Telbivudine for the management of chronic hepatitis B virus infection. Clin Ther. 2007 Dec;29(12):2635-53. [Pubmed] ; Amarapurkar DN: Telbivudine: a new treatment for chronic hepatitis B. World J Gastroenterol. 2007 Dec 14;13(46):6150-5. [Pubmed] ; Dusheiko G, Danta M: Telbivudine for the treatment of chronic hepatitis B. Drugs Today (Barc). 2007 May;43(5):293-304. [Pubmed] ; Keam SJ: Telbivudine. Drugs. 2007;67(13):1917-29. [Pubmed] ; Ruiz-Sancho A, Sheldon J, Soriano V: Telbivudine: a new option for the treatment of chronic hepatitis B. Expert Opin Biol Ther. 2007 May;7(5):751-61. [Pubmed] ; Marcellin P, Asselah T, Boyer N: Treatment of chronic hepatitis B. J Viral Hepat. 2005 Jul;12(4):333-45. [Pubmed] ; Han SH: Telbivudine: a new nucleoside analogue for the treatment of chronic hepatitis B. Expert Opin Investig Drugs. 2005 Apr;14(4):511-9. [Pubmed] ; Jones R, Nelson M: Novel anti-hepatitis B agents: A focus on telbivudine. Int J Clin Pract. 2006 Oct;60(10):1295-9. [Pubmed]
• External Links: RxList; Drugs.com

Selleck Chemicals - S1651

Research Area: Infection
Biological Activity:
Telbivudine(Tyzeka, Sebivo) is an antiviral drug used in the treatment of hepatitis B infection. Clinical trials have shown it to be significantly more effective than lamivudine or adefovir, and less likely to cause resistance. Telbivudine is a synthetic thymidine nucleoside analogue; it is the L-isomer of thymidine. It is taken once daily. [1]

REFERENCES

• Keam SJ: Telbivudine. Drugs. 2007;67(13):1917-29. Pubmed
• Matthews SJ: Telbivudine for the management of chronic hepatitis B virus infection. Clin Ther. 2007 Dec;29(12):2635-53. Pubmed
• Dusheiko G, Danta M: Telbivudine for the treatment of chronic hepatitis B. Drugs Today (Barc). 2007 May;43(5):293-304. Pubmed
• Ruiz-Sancho A, Sheldon J, Soriano V: Telbivudine: a new option for the treatment of chronic hepatitis B. Expert Opin Biol Ther. 2007 May;7(5):751-61. Pubmed
• Marcellin P, Asselah T, Boyer N: Treatment of chronic hepatitis B. J Viral Hepat. 2005 Jul;12(4):333-45. Pubmed
• Han SH: Telbivudine: a new nucleoside analogue for the treatment of chronic hepatitis B. Expert Opin Investig Drugs. 2005 Apr;14(4):511-9. Pubmed
• Jones R, Nelson M: Novel anti-hepatitis B agents: A focus on telbivudine. Int J Clin Pract. 2006 Oct;60(10):1295-9. Pubmed
• Amarapurkar DN: Telbivudine: a new treatment for chronic hepatitis B. World J Gastroenterol. 2007 Dec 14;13(46):6150-5. Pubmed
• http://en.wikipedia.org/wiki/Telbivudine