Telbivudine, 替比夫定

L-Thymidine

Telbivudine is a β-L-nucleoside analog of thymidine that has antiviral activity. It is active against hepatitis B virus (HBV) in 2.2. 5 cells (EC50 = 0.19 μM). Telbivudine is selective for HBV over HIV-1, herpes simplex virus-1 (HSV-1), HSV-2, and influenza A and B (EC50s = >100 μM). It reduces serum viral load in a woodchuck model of chronic HBV infection in a dose-dependent manner. Formulations containing telbivudine have been used in the treatment of chronic HBV infection.

Nucleoside analog; specific inhibitor of hepatitis B virus (HBV) replication. Antiviral.

Telbivudine is a synthetic thymidine nucleoside analogue with antiviral activity highly specific for the treatment of hepatitis B virus (HBV). Intracellularly, telbivudine is phosphorylated to its active metabolite, telbivudine triphosphate. The dideoxy telbivudine triphosphate competes with thymidine for incorporation into viral DNA, thereby causing DNA chain termination and inhibiting the function of HBV DNA polymerase (reverse transcriptase). This results in the blockade of HBV DNA replication and viral propagation.

Telbivudine is a nucleoside analogue and antiviral inhibitor of hepatitis B virus (HBV) replication which is used alone and in combination with other agents in the therapy of the hepatitis B. Telbivudine does not appear to be a significant cause of drug induced liver injury, but can be associated with flares of the underlying hepatitis B either during therapy or upon withdrawal.

Telbivudine, also known as beta-L-thymidine or tyzeka, belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. Pyrimidine 2'-deoxyribonucleosides are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2. Telbivudine is a drug which is used 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. Telbivudine is soluble (in water) and a very weakly acidic compound (based on its pKa). Telbivudine has been detected in multiple biofluids, such as urine and blood. Within the cell, telbivudine is primarily located in the cytoplasm. Telbivudine can be biosynthesized from thymine.

L-Thymidine is an antiviral drug that is used in the treatment of chronic hepatitis. It has been shown to be active against a range of viruses, including HIV, HSV, and HBV. L-Thymidine can also be used to treat patients with cancer as an anti-cancer agent. L-Thymidine is a prodrug that is converted into thymidine triphosphate (TTP), which inhibits viral DNA polymerase by competitive inhibition. The antiviral activity of L-Thymidine may be due to its ability to inhibit the synthesis of viral proteins required for viral replication by interfering with the protein production process or by inhibiting the formation of dsDNA during reverse transcription.

Title: Telbivudine

CAS Registry Number: 3424-98-4

CAS Name: 1-(2-Deoxy-b-L-erythro-pentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione

Additional Names: 1,2'-deoxy-b-L-ribofuranosylthymine; 2'-deoxy-L-thymidine; LdT; L-thymidine

Molecular Formula: C10H14N2O5

Molecular Weight: 242.23

Percent Composition: C 49.58%, H 5.83%, N 11.56%, O 33.03%

Literature References: Nucleoside analog; specific inhibitor of hepatitis B virus (HBV) replication. Prepn: J. Smejkal, F. Sorm, Collect. Czech. Chem. Commun. 29, 2809 (1964); A. Holy, ibid. 37, 4072 (1972). Anti-HBV activity: M. L. Bryant et al., Nucleosides Nucleotides Nucleic Acids 20, 597 (2001). In vitro pharmacology: B. Hernandez-Santiago et al., Antimicrob. Agents Chemother. 46, 1728 (2002). Clinical evaluation in hepatitis B: C.-L. Lai et al., Hepatology 40, 719 (2004). Review of mechanism of action and pharmacology: D. N. Standring et al., Antiviral Chem. Chemother. 12, Suppl. 1, 119-129 (2001); of clinical development: S.-H. B. Han, Expert Opin. Invest. Drugs 14, 511-519 (2005). See also Thymidine.

Properties: Crystals from ethanol, mp 186°(Smejkal, Sorm). [a]D20 -20.3° (c = 0.192 in water). Also reported as mp 189° (Holy). uv max (pH 2): 267 nm (e 9800).

Melting point: mp 186°; mp 189°

Optical Rotation: [a]D20 -20.3° (c = 0.192 in water)

Absorption maximum: uv max (pH 2): 267 nm

Therap-Cat: Antiviral.

Keywords: Antiviral; Purines/Pyrimidinones.