Clevudine

Clevudine Basic information

Product Name:

Clevudine

Synonyms:

CLEVUDINE;1-(2'-DEOXY-2'-FLUORO-BETA-L-ARABINOFURANOSYL)-5-METHYLURACIL;CLEVUDINE, 1-(2'-DEOXY-2'-FLUORO-β-L-ARABINOFURANOSYL)-5-METHYLURACIL;1-[(2S,3R,4S,5S)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione;2'-Fluoro-5-methylarabinosyluracil;Levovir;1-(2''-DEOXY-2''-FLUORO--L-ARABINOFURANOSYL)-5-METHYLURACIL;CLEVUDINE: 1-(2''-DEOXY-2''-FLUORO-BETA-L-ARABINOFURANOSYL)-5-METHYLURACIL

CAS:

MF:

C10H13FN2O5

MW:

260.22

EINECS:

 

Product Categories:

API;Bases & Related Reagents;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals;Inhibitors

Mol File:

163252-36-6.mol

 

Clevudine Chemical Properties

Melting point 

184-185°

alpha 

D25 -111.77° (c = 0.23 in methanol)

 

Safety Information

Toxicity

LD50 in mice, rats (mg/kg): >5000, >3000 orally (Painter)

MSDS Information

 

Clevudine Usage And Synthesis

Description

Clevudine is a fluorinated b-L-nucleoside analog launched for the oral treatment of chronic HBV infection. It is the fifth nucleoside or nucleotide analog to be marketed for this indication. The previous drugs from this class include lamivudine, adefovir, entecavir, and telbivudine. In HBV-expressing human hepatoma cell line 2.2.15, clevudine inhibits HBV DNA synthesis with an EC₅₀ of 0.1 μM, and does not show cytotoxicity up to 200 μM. It is phosphorylated by cellular kinases to the active triphosphate derivative, which subsequently inhibits HBV DNA polymerase and HBV replication. 466 Shridhar Hegde and Michelle Schmidt Clevudine-5′-triphosphate has an intracellular half-life of 16.5 h. Interestingly, it is a non-competitive inhibitor of viral polymerase, and inhibits HBV replication without being incorporated into the DNA. The pharmacokinetic profile of clevudine was linear with a plasma half-life of approximately 60 h. Clevudine was undetectable in plasma after 4 weeks following the cessation of dosing.The most common adverse events reported with clevudine treatment include infection, asthenia, dyspepsia, abdominal pain, headache, and diarrhea.
Clevudine is chemically derived from L-ribose by first incorporating acyl protective groups to produce 1-O-acetyl-2,3,5-tri-O-benzoyl-b-L-ribofuranose intermediate, which is then converted to 1,3,5-tri-O-benzoyl-a-L-ribofuranose in two steps by treating To Market, To Market 2007 467 with hydrogen chloride and subsequent hydrolysis and acyl migration. The remaining steps leading to clevudine include conversion of the C2-hydroxy group to C2-fluoro group with triethylamine trihydrofluoride, formation of the corresponding ribofuranosyl bromide intermediate with hydrogen bromide and acetic acid, condensation with silylated thymine, and removal of benzoyl protective groups with methanolic ammonia.

Chemical Properties

White Solid

Originator

University of Georgia/ Yale University (US)

Uses

Antiviral drug, used for the treatment of Hepatitis B.

Brand name

Levovir