U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C11H13BrN2O5
Molecular Weight 333.135
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of BRIVUDINE

SMILES

OC[C@H]1O[C@H](C[C@@H]1O)N2C=C(\C=C\Br)C(=O)NC2=O

InChI

InChIKey=ODZBBRURCPAEIQ-PIXDULNESA-N
InChI=1S/C11H13BrN2O5/c12-2-1-6-4-14(11(18)13-10(6)17)9-3-7(16)8(5-15)19-9/h1-2,4,7-9,15-16H,3,5H2,(H,13,17,18)/b2-1+/t7-,8+,9+/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.drugs.com/international/brivudine.html | https://www.ncbi.nlm.nih.gov/pubmed/19281225 | https://www.ncbi.nlm.nih.gov/pubmed/17948980 | https://www.ncbi.nlm.nih.gov/pubmed/21833720

Brivudine (trade names Zostex, Mevir, Brivir, among others) is an antiviral drug used in the treatment of herpes zoster ("shingles"). Brivudine is an analog of the nucleoside thymidine. The active compound is brivudine 5'-triphosphate, which is formed in subsequent phosphorylations by viral (but not human) thymidine kinase and presumably by the nucleoside-diphosphate kinase. Brivudine 5'-triphosphate works because it is incorporated into the viral DNA, but then blocks the action of DNA polymerases, thus inhibiting viral replication. Brivudine is used for the treatment of herpes zoster in adult patients. It is taken orally once daily, in contrast to aciclovir, valaciclovir, and other antivirals. A study has found that it is more effective than aciclovir, but this has been disputed because of a possible conflict of interest on part of the study authors. The drug is contraindicated in patients undergoing immunosuppression (for example because of an organ transplant) or cancer therapy, especially with fluorouracil (5-FU) and chemically related (pro)drugs such as capecitabine and tegafur, as well as the antimycotic drug flucytosine, which is also related to 5-FU. It has not been proven to be safe for children and pregnant or breastfeeding women. The drug is generally well tolerated. The only common side effect is nausea (in 2% of patients). Less common side effects (<1%) include a headache, increased or lowered blood cell counts (granulocytopenia, anemia, lymphocytosis, monocytosis), increased liver enzymes, and allergic reactions. Brivudine is approved for use in a number of European countries including Austria, Belgium, Germany, Greece, Italy, Portugal, Spain, and Switzerland.

Originator

Sources: Zeitschrift fuer die Gesamte Experimentelle Medizin (1925), 47, 211-21.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
240.0 nM [Ki]
29.0 µM [EC50]
80.0 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Brivox

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Anti-herpes simplex virus and anti-human cell growth activity of E-5-propenyl-2'-deoxyuridine and the concept of selective protection in antivirus chemotherapy.
1980 Dec
Selective inhibition of herpesvirus deoxyribonucleic acid synthesis by acycloguanosine, 2'-fluoro-5-iodo-aracytosine, and (E)-5-(2-bromovinyl)-2'-deoxyuridine.
1981 May
Antiherpes activity of [E]-5-(1-propenyl)-2'-deoxyuridine and 5-(1-propenyl)-1-beta-D-arabinofuranosyluracil.
1981 Nov
Inhibitory effects of antiherpesviral thymidine analogs against varicella-zoster virus.
1982 Feb
In vitro susceptibility of varicella-zoster virus to E-5-(2-bromovinyl)-2'-deoxyuridine and related compounds.
1982 Jan
Antiherpes activity of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil and some other 5-substituted uracil arabinosyl nucleosides in two different cell lines.
1983 Sep
In vitro and in vivo antiviral activity of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and related compounds.
1984 Jun
Selective in vitro and in vivo activities of 5-(2-haloalkyl)pyrimidine nucleoside analogs, particularly 5-(2-chloroethyl)-2'-deoxyuridine, against herpes simplex virus.
1985 Aug
Comparative efficacy and selectivity of some nucleoside analogs against Epstein-Barr virus.
1985 Jun
Synthesis and antiviral activity of the carbocyclic analogues of (E)-5-(2-halovinyl)-2'-deoxyuridines and (E)-5-(2-halovinyl)-2'-deoxycytidines.
1985 May
In vitro and in vivo antiviral activity of 2'-fluorinated arabinosides of 5-(2-haloalkyl)uracil.
1987 Jun
Novel acyclic adenosine analogs inhibit Epstein-Barr virus replication.
1987 Sep
Comparison of two bromovinyl nucleoside analogs, 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil and E-5-(2-bromovinyl)-2'-deoxyuridine, with acyclovir in inhibition of Epstein-Barr virus replication.
1988 Jul
Phosphonoformate and phosphonoacetate derivatives of 5-substituted 2'-deoxyuridines: synthesis and antiviral activity.
1988 Sep
Antiviral and antitumor structure-activity relationship studies on tetracyclic eudistomines.
1992 Aug 21
Antiviral activity of selected acyclic nucleoside analogues against human herpesvirus 6.
1995 Dec
Understanding the binding of 5-substituted 2'-deoxyuridine substrates to thymidine kinase of herpes simplex virus type-1.
1996 Nov 22
Antiviral efficacies of famciclovir, valaciclovir, and brivudin in disseminated herpes simplex virus type 1 infection in mice.
1997
Structure-activity relationship of the affinity of 5-substituted uracil nucleoside analogues for varicella-zoster virus thymidine kinase and their activity against varicella-zoster virus.
1997 Aug
Efficacy of select antivirals against Cryptosporidium parvum in vitro.
1998 Nov 1
Hydroxyurea potentiates the antiherpesvirus activities of purine and pyrimidine nucleoside and nucleoside phosphonate analogs.
1999 Dec
A rapid phenotypic assay for detection of acyclovir-resistant varicella-zoster virus with mutations in the thymidine kinase open reading frame.
2000 Apr
The cyclohexene ring system as a furanose mimic: synthesis and antiviral activity of both enantiomers of cyclohexenylguanine.
2000 Feb 24
Antiviral activity of ganciclovir elaidic acid ester against herpesviruses.
2000 Mar
Anti-(herpes simplex virus) activity of 4'-thio-2'-deoxyuridines: a biochemical investigation for viral and cellular target enzymes.
2000 Oct 15
Novel carbocyclic nucleosides containing a cyclobutyl ring: adenosine analogues.
2001 Sep
A thymidine phosphorylase-stable analogue of BVDU with significant antiviral activity.
2002 Dec 5
Chemotherapy of varicella-zoster virus by a novel class of highly specific anti-VZV bicyclic pyrimidine nucleosides.
2002 Jul 18
Lack of susceptibility of bicyclic nucleoside analogs, highly potent inhibitors of varicella-zoster virus, to the catabolic action of thymidine phosphorylase and dihydropyrimidine dehydrogenase.
2002 May
Comparative study of purine and pyrimidine nucleoside analogues acting on the thymidylate kinases of Mycobacterium tuberculosis and of humans.
2003 Aug 4
Amino acid changes within conserved region III of the herpes simplex virus and human cytomegalovirus DNA polymerases confer resistance to 4-oxo-dihydroquinolines, a novel class of herpesvirus antiviral agents.
2003 Feb
Enzymatic and structural analysis of inhibitors designed against Mycobacterium tuberculosis thymidylate kinase. New insights into the phosphoryl transfer mechanism.
2003 Feb 14
In vitro activity of potential anti-poxvirus agents.
2003 Jan
Evaluation of antiviral activity against human herpesvirus 8 (HHV-8) and Epstein-Barr virus (EBV) by a quantitative real-time PCR assay.
2004 Jun
In vitro selection of drug-resistant varicella-zoster virus (VZV) mutants (OKA strain): differences between acyclovir and penciclovir?
2004 Mar
Human herpesvirus 6 DNA polymerase: enzymatic parameters, sensitivity to ganciclovir and determination of the role of the A961V mutation in HHV-6 ganciclovir resistance.
2004 Oct
Synthesis and in vitro anti-mycobacterial activity of 5-substituted pyrimidine nucleosides.
2005 Dec 15
Antiadenovirus activities of several classes of nucleoside and nucleotide analogues.
2005 Mar
Synthesis of some new benzisothiazolone and benzenesulfonamide derivatives of biological interest starting from saccharin sodium.
2013 Oct
Patents

Sample Use Guides

Brivudin was given as one 125-mg tablet every 6 hours.
Route of Administration: Oral
HT1080 cells were treated with Gemcitabine (10 ng/ml) with and without RP101 (Brivudine) (30 mkM). After trypsinisation, the number of living cells was determined using the Cell Counter and Analyzer System CASY TT (Schärfe System GmbH, Reutlingen, Germany). The treatment of HT-1080 cells with Gemcitabine together with RP101 reduced penetration through matrigel by 30–50% compared to cells treated with Gemcitabine alone
Name Type Language
BRIVUDINE
INN   MART.   MI   WHO-DD  
INN  
Official Name English
brivudine [INN]
Common Name English
BRIVUDIN
Common Name English
NSC-633770
Code English
BVDU
Common Name English
BRIVUDINE [MI]
Common Name English
Brivudine [WHO-DD]
Common Name English
BRIVUDINE [MART.]
Common Name English
RP101
Code English
ZOSTEX
Brand Name English
RP-101
Code English
5-((E)-2-BROMOVINYL)-2'-DEOXYURIDINE
Systematic Name English
Classification Tree Code System Code
WHO-ATC J05AB15
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
FDA ORPHAN DRUG 247807
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
NCI_THESAURUS C471
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
EU-Orphan Drug EU/3/09/703
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
NCI_THESAURUS C281
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
NCI_THESAURUS C1557
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
WHO-VATC QJ05AB15
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL31634
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
PRIMARY
SMS_ID
100000088646
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PRIMARY
INN
6267
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PRIMARY
CAS
69304-47-8
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PRIMARY
DRUG CENTRAL
397
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PRIMARY
EVMPD
SUB05893MIG
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PRIMARY
NCI_THESAURUS
C67088
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PRIMARY
DRUG BANK
DB03312
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PRIMARY
PUBCHEM
446727
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
PRIMARY
NSC
633770
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
PRIMARY
MERCK INDEX
m2655
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
PRIMARY Merck Index
RXCUI
59161
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PRIMARY RxNorm
MESH
C020235
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
PRIMARY
WIKIPEDIA
Brivudine
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
PRIMARY
EPA CompTox
DTXSID0045755
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
PRIMARY
FDA UNII
2M3055079H
Created by admin on Sat Dec 16 15:59:20 GMT 2023 , Edited by admin on Sat Dec 16 15:59:20 GMT 2023
PRIMARY