163252-36-6 Usage
Description
Clevudine, also known by its brand name Levovir, is a fluorinated β-L-nucleoside analog that serves as an antiviral drug. It is specifically designed for the oral treatment of chronic Hepatitis B Virus (HBV) infection and is the fifth nucleoside or nucleotide analog to be marketed for this purpose. Clevudine effectively inhibits HBV DNA synthesis without exhibiting cytotoxicity and is chemically derived from L-ribose, resulting in a white solid form.
Uses
Used in Pharmaceutical Industry:
Clevudine is used as an antiviral drug for the treatment of chronic Hepatitis B. It works by inhibiting HBV DNA synthesis with an EC50 of 0.1 μM and does not show cytotoxicity up to 200 μM. The drug is phosphorylated by cellular kinases to its active triphosphate derivative, which then inhibits HBV DNA polymerase and HBV replication. Clevudine-5′-triphosphate has an intracellular half-life of 16.5 hours and acts as a non-competitive inhibitor of viral polymerase, inhibiting HBV replication without being incorporated into the DNA.
The pharmacokinetic profile of clevudine is linear, with a plasma half-life of approximately 60 hours. It is 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.
Originator
University of Georgia/
Yale University (US)
Synthesis
The synthesis is depicted in
the scheme. L-Arabinose (27) was treated with acetic
anhydride and pyridine at room temperature for four hours to give acetylated arabinose, which was then brominated using
30% HBr in AcOH/Ac2O at room temperature for 36 hours
to afford bromo-sugar 28 as a white solid in 57% yield after
crystallization in ethyl ether. Bromo-sugar 28 was then
treated with Zn dust, CuSO4 and NaOAc in AcOH/H2O, followed
by chromatographic separation to give L-arabinal 29
in 60% yield. L-arabinal 29 was converted to the fluoro derivative
in 70% crude yield by reaction with Selectfluor? (FTEDA-
BF4) in refluxing nitromethane/H2O, and the resulting
fluoroalcohol was deacetylated with NaOMe in MeOH to
give compound 30 in 100% crude yield. Compound 30 was
then treated with H2SO4 in refluxing MeOH to afford methyl
furanoside 31 in 80% crude yield. Furanoside 31 was benzoylated
with benzoyl chloride in pyridine to give a mixture
of isomers, from which the α-anomer was isolated by chromatography
and then brominated with 30% HBr/AcOH in
CH2Cl2 to provide the crude bromo-sugar 32 which was dissolved
in chloroform and used without further purification in
the next step. Compound 34 was obtained by treatment of
thymine (33) with HMDS and ammonium sulfate in refluxing
chloroform for 16 hours. The sugar 32 was condensed with
silylated pyrimidine derivative 34 in refluxing chloroform to
afford 3,5-di-O-benzoylclevudine in 42% yield after recrystallization
from ethanol. The benzoyl groups were removed
upon treatment with n-butylamine in refluxing
methanol to give clevudine (IV) in 82% yield.
Check Digit Verification of cas no
The CAS Registry Mumber 163252-36-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,6,3,2,5 and 2 respectively; the second part has 2 digits, 3 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 163252-36:
(8*1)+(7*6)+(6*3)+(5*2)+(4*5)+(3*2)+(2*3)+(1*6)=116
116 % 10 = 6
So 163252-36-6 is a valid CAS Registry Number.
InChI:InChI=1/C10H13FN2O5/c1-4-2-13(10(17)12-8(4)16)9-6(11)7(15)5(3-14)18-9/h2,5-7,9,14-15H,3H2,1H3,(H,12,16,17)/t5-,6+,7-,9-/m0/s1
163252-36-6Relevant articles and documents
A general synthesis of 2′-deoxy-2′-[18F]fluoro-1-β-D- arabinofuranosyluracil and its 5-substituted nucleosides
Alauddin, Mian M.,Conti, Peter S.,Fissekis, John D.
, p. 285 - 289 (2003)
Several 2′-deoxy-2′-[18F]fluoro-1-β-D- arabinofuranosyluracil derivatives have been synthesized. Coupling of 1-bromo-2-deoxy-2-[18F]fluoro-3,5-di-O-benzoyl-α-D- arabinofuranose 2 with protected uracil derivatives 3a-e followed by hydrolysis and high-performance liquid chromatography purification produced the radiolabeled nucleosides 4a-e in 15-30% yield (d. c.), > 99% radiochemical purity and 55.5-103.6 GBq/μmol specific activities. Copyright
Regio- and stereoselective syntheses of L-pentose derivatives from L-arabinose
Sivets, Grigorii G.
, p. 920 - 931 (2018)
Novel L-arabinose, L-ribose, 2-deoxy-L-ribose and 2-fluoro-2-deoxy-L-arabinose derivatives were synthesized from readily available L-arabinose. Different synthetic routes to methyl 3,5-di-O-acylated-L-arabino(ribo)furanosides as valued intermediates for t
MODIFIED OLIGOMERIC COMPOUNDS AND USES THEREOF
-
Page/Page column 83; 88, (2021/02/19)
The present disclosure provides oligomeric compounds comprising a modified oligonucleotide having at least one stereo-non-standard nucleoside. An oligomeric compound comprising a modified oligonucleotide consisting of 12-30 linked nucleosides, wherein at least one nucleoside of the modified oligonucleotide is a stereo-non-standard nucleoside; and wherein the oligomeric compound is selected from among an RNAi compound, a modified CRISPR compound, and an artificial mRNA compound.
A green synthetic clevudine pharmaceutical intermediates
-
, (2019/03/29)
The invention relates to a green synthetic clevudine pharmaceutical intermediates method, comprises the following steps: The formula II compound is dissolved in the organic solvent, under ice bath by adding 40% of the hydrobromic, tetrabutyl ammonium fluo