| Identification | More | [Name]
Abacavir | [CAS]
136470-78-5 | [Synonyms]
[(1s,4r)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]-1-cyclopent-2-enyl]methanol
[(1S,4R)-4-(2-AMINO-6-CYCLOPROPYLAMINO-PURIN-9-YL)-CYCLOPENT-2-ENYL]-METHANOL
(+/-)-4-[2-amino-6-(cyclopropylamino)-9h-purin-9-yl]-2-cyclopentene-1-methanol
ABACAVIR
1592u89
2-Cyclopentene-1-methanol, 4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-, (1S,4R)-
2-Cyclopentene-1-methanol, 4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-, (1S-cis)-
(+/-)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol
Abacavir | [EINECS(EC#)]
620-487-9 | [Molecular Formula]
C14H18N6O | [MDL Number]
MFCD00903850 | [Molecular Weight]
286.33 | [MOL File]
136470-78-5.mol |
| Hazard Information | Back Directory | [Description]
The drug is extensively metabolized via stepwise phosphorylation to 5′-mono-, di-, and triphosphate. Abacavir is well absorbed (>75%) and penetrates the CNS. The drug can be taken without regard to meals. The drug does not show any clinically significant drug–drug interactions. Abacavir has been reported to produce life-threatening hypersensitivity reactions. The major use of abacavir appears to be in combination with other nucleoside RT inhibitors. A fixed-combination product has recently been approved by the U.S. FDA consisting of 300 mg of ABC, 150 mg of 3TC, and 300 mg of ZDV (Trizivar). The combination has been shown to be superior to other combinations in reducing viral load as well as to show improvement in CD4 cell count. | [Originator]
Ziagen
,GlaxoSmithKline | [Uses]
A nucleoside reverse transcriptase inhibitor (NRTI). | [Uses]
Abacavir is a commonly used nucleoside analogue with potent antiviral activity against HIV-1. - See more at: http://www.selleckchem.com/products/abacavir-sulfate.html#sthash.lApvcTNO.dpuf | [Definition]
ChEBI: Abacavir is a 2,6-diaminopurine that is (1S)-cyclopent-2-en-1-ylmethanol in which the pro-R hydrogen at the 4-position is substituted by a 2-amino-6-(cyclopropylamino)-9H-purin-9-yl group. A nucleoside analogue reverse transcriptase inhibitor (NRTI) with antiretroviral activity against HIV, it is used (particularly as the sulfate) with other antiretrovirals in combination therapy of HIV infection. It has a role as a HIV-1 reverse transcriptase inhibitor, an antiviral drug and a drug allergen. | [Indications]
Abacavir (Ziagen) is a guanosine nucleoside analogue
indicated for the therapy of HIV-1 infection in adults
and children. It is used as part of a multidrug regimen
and is available in a fixed-dose combination with zidovudine
and lamivudine (Trizivir). It is also used for
postexposure HIV infection prophylaxis. | [Manufacturing Process]
Treatment of 2,5-diamino-4,6-dihydroxypyrimidine (I) with
(chloromethylene)dimethylammonium chloride yielded the dichloropyrimidine
with both amino groups derivatized as amidines. Partial hydrolysis with
aqueous HCl in hot ethanol gave N-(2-amino-4,6-dichloro-pyrimidin-5-yl)-N,Ndimethylformamidene
(II). Subseqent buffered hydrolysis at pH 3.2 yielded
the (2-amino-4,6-dichloro-pyrimididin-5-ylamino)acetaldehyde (III).
Condensation chloropyrimidine (III) with (1S,4R)-4-amino-2-cyclopentene-1-
methanol (IV) in the presence of triethylamine and NaOH gave [2-amino-4-
chloro-6-(4-hydroxymethyl-cyclopent-2-enylamino)pyrimidin-5-ylamino]-
acetaldehyde (V). The correct enantiomer (IV) of racemic aminocyclopentene
was obtained by resolution of diastereomeric salts with D-dibenzoyltartaric
acid. Cyclization of (V) to the corresponding purine was accomplished with
refluxing triethyl orthoformate or diethoxymethyl acetate to give nucleoside
analogue [4-(2-amino-6-chloro-purin-9-yl)-cyclopent-2-enyl]methanol (VI).
Displacement of chloride in the purine nucleus with cyclopropyl amine in
refluxing butanol afforded abacavir. The structure of obtained compound was
confirmed by 1H NMR method and elemental analysis.
In practice it is usually used as sulfate salt. | [Therapeutic Function]
Antiviral | [Antimicrobial activity]
Abacavir has activity against HIV-1, HIV-2 and human T-cell
lymphotrophic virus type-1 (HTLV-1). | [Acquired resistance]
Resistance is associated with specific changes in codons 184
with 65, 74 or 115 in the HIV reverse transcriptase codon
region. | [General Description]
Abacavir is a nucleoside reverse transcriptase inhibitorNRTI that has been approved for use in combination therapiesfor the treatment of HIV and AIDS. Once in the tissues,it is metabolized by stepwise phosphorylation to themonophosphate, diphosphate, and triphosphate. Abacavir ishighly bioavailable (＞75%) and is effective by the oralroute. It penetrates the blood-brain barrier efficiently.Abacavir has been reported to produce life-threatening hypersensitivityreactions in some patients. | [Pharmaceutical Applications]
A synthetic analog of guanine formulated for oral use. | [Pharmacokinetics]
Oral absorption: 83%
Cmax 300 mg oral, twice daily: 3.0 ± 0.89 mg/L
600 mg once daily: 4.26 mg/L
Plasma half-life: 1.5 h
Volume of distribution: 0.8 L/kg
Plasma protein binding: c. 49%
Absorption
After oral administration abacavir sulfate undergoes rapid and extensive absorption unaffected by food.
Distribution
It penetrates well into the cerebrospinal fluid (CSF) and is an NRTI of choice if this characteristic is thought desirable. Good penetration into the male genital tract has been observed. The drug is secreted into human breast milk.
Metabolism
It is primarily metabolized in the liver, mainly by alcohol dehydrogenase and glucuronidation.
Excretion
Around 83% of the dose is eliminated in the urine, <2% as unchanged drug; the remainder is excreted in the feces. Dose adjustment is unnecessary in renal impairment. It can be used in moderate hepatic impairment, but is contraindicated if dysfunction is severe. | [Clinical Use]
Treatment of HIV infection in adults and children (in combination with
other antiretroviral drugs) | [Side effects]
Abacavir is associated with side effects such as
anorexia, nausea, vomiting, malaise, headache, and insomnia.
A potentially fatal hypersensitivity reaction develops
in approximately 5% of patients, usually early in
the course of treatment. Fever and rash are the most
common symptoms of this reaction; malaise, respiratory
symptoms, and gastrointestinal complaints may also occur.
Resistance to abacavir may be associated with resistance
to zidovudine, didanosine, and lamivudine. | [Side effects]
Life-threatening hypersensitivity reactions occur in 5–8%
of all individuals, necessitating discontinuation of the drug.
Typically patients present within the first 6 weeks of starting
treatment with fever, rash or other symptoms that worsen
in severity with continued drug exposure. Hypersensitivity
is associated with carriage of the major histocompatibility
complex class I allele HLA-B57*01 and screening for this
allele can significantly reduce the incidence
of this effect.
Current or recent (within the preceding 6 months) use of
abacavir has been associated with a risk of myocardial infarction,
but studies have yielded conflicting data. | [Drug interactions]
Potentially hazardous interactions with other drugs
Antivirals: possibly reduces effects of ribavirin;
concentration reduced by tipranavir.
Orlistat: absorption possibly reduced by orlistat. | [Metabolism]
Abacavir is primarily metabolised by the liver with
approximately 2% of the administered dose being renally
excreted, as unchanged compound. The primary pathways
of metabolism in man are by alcohol dehydrogenase and
by glucuronidation to produce the 5'-carboxylic acid
and 5'-glucuronide which account for about 66% of the
administered dose. The metabolites are excreted in the
urine. |
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