CAS 7481-89-2|DDC|zalcitabine|4-amino-1-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one|DDCYD|Dideoxycytidine|HIVID|Zalcitabine|扎西他滨|Hivid|NSC 606170|2′,3′-Dideoxycytidine|2'...

General Information

Structure

Molecular Formula

C₉H₁₃N₃O₃

Molecular Mass

211.21782

Exact Mass

211.09569129

Charge

InChI

InChI=1S/C9H13N3O3/c10-7-3-4-12(9(14)11-7)8-2-1-6(5-13)15-8/h3-4,6,8,13H,1-2,5H2,(H2,10,11,14)/t6-,8+/m0/s1

InChIKey

WREGKURFCTUGRC-POYBYMJQSA-N

Canonic Smiles

Nc1ccn(c(=O)n1)[C@H]1CC[C@H](O1)CO

Isomeric Smiles

O1[C@@H](n2ccc(nc2=O)N)CC[C@H]1CO

Calculated Properties

JChem

LogD (pH = 7.4)

-1.19

LogD (pH = 5.5)

-1.19

Log P

-1.19

Rotatable Bonds

H Donor

H Acceptors

Lipinski's Rule of Five

true

Acid pKa

2.88

Polar Surface Area

88.15

Polarizability

20.75

Molar Refractivity

52.24

LOG S

-0.73

Data Source

Names and Identifiers

Synonyms

DDCYDDDCZalcitabineDideoxycytidine扎西他滨2′,3′-DideoxycytidineHividNSC 6061702',3'-二脱氧胞啶Zalcitabine2',3'-Dideoxycytidine2',3'-DIDEOXYCYTIDINE2’,3’-DideoxycytidineRo 24-2027/000DDCDideoxycytidinezalcitabine4-amino-1-[(2R,5S)-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2(1H)-oneDDCYD2',3'-Dideoxycytidine

IUPAC Traditional name

zalcitabine

Brand Name

HIVID

IUPAC name

4-amino-1-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one

API Name

Zalcitabine

International Nonproprietary Name (INN)

zalcitabine

Names and Identifiers

Registration numbers

CAS Number

7481-89-2

MDL Number

MFCD00012188

PubChem SID

24278377465078792486283416096428287322635

Beilstein Number

Merck Index

PubChem CID

DrugBank ID

UniProt Database

P12502P27718P48861Q1A267Q62674P35963P12497Q9QBY3Q9Q720Q75002Q8AII1P22382P19505O89940O41798

BKMS React Database

23785159816590715342315441227

BRENDA Ligand Database

23781659072715342315441251598

CompTox Database

DTXSID0023747

PubMed Citation Links

119059887727578

Drug Central Database

2,856

CHEMBL

CHEMBL853

SureChEMBL Database

SCHEMBL3598

BRENDA Database

3.5.4.52.7.1.742.7.1.212.7.1.763.1.26.132.4.2.62.7.7.492.7.1.1457.1.1.22.7.7.317.6.2.22.7.2.3

Reaxys Registry

654956

MetaboLights Database

MTBLS1693MTBLS379MTBLS867MTBLS926MTBLS2878MTBLS746MTBLS673

Wikipedia Title

SABIO-RK Database

KEGG DRUG Database

ACToR Database

KEGG ID

CHEBI ID

HMDB Database

LINCS Database

Registration numbers

Properties

Safety Information

-20°C

Refrigerator

Respiratory sensitization, category 1

Germ cell mutagenicity, categories 1A,1B,2

Carcinogenicity, categories 1A,1B,2

Reproductive toxicity, categories 1A,1B,2

Specific Target Organ Toxicity – Single exposure, categories 1,2

Specific Target Organ Toxicity – Repeated exposure, categories 1,2

Aspiration Hazard, category 1

Properties

Related Proteins

No Data Available

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Molecular Spectra

No Data Available

Click here to submit data

Molecule Details

DrugBank

DB00943

Drug Groups

approved

Description

A dideoxynucleoside compound in which the 3'-hydroxyl group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of 5' to 3' phosphodiester linkages, which are needed for the elongation of DNA chains, thus resulting in the termination of viral DNA growth. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [PubChem]

Indication

For the treatment of Human immunovirus (HIV) infections in conjunction with other antivirals.

Pharmacology

Zalcitabine is an analog of 2'-deoxycytidine that is pharmacologically related to but structurally different from other nucleotide reverse transcriptase inhibitors (NRTIs). Zalcitabine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.

Toxicity

Acute overdose: Inadvertent pediatric overdoses have occurred with doses up to 1.5 mg/kg zalcitabine. Chronic overdose: in an initial dose-finding study in which zalcitabine was administered at doses 25 times (0.25 mg/kg every 8 hours) the currently recommended dose, one patient discontinued zalcitabine after 1? weeks of treatment subsequent to the development of a rash and fever.

Affected Organisms

Human Immunodeficiency Virus

Biotransformation

Hepatic

Absorption

Bioavailability is over 80% following oral administration.

Half Life

2 hours

Protein Binding

Less than 4%

Elimination

Renal excretion of unchanged drug appears to be the primary route of elimination, accounting for approximately 80% of an intravenous dose and 60% of an orally administered dose within 24 hours after dosing (n=19). Renal clearance exceeds glomerular filtration rate suggesting renal tubular secretion contributes to the elimination of zalcitabine by the kidneys.

Distribution

* 0.304 to 0.734 L/kg

Clearance

* 285 mL/min [HIV-infected patients receiving 1.5 mg IV infusion for 1 hour]

References

• Shelton MJ, O'Donnell AM, Morse GD: Zalcitabine. Ann Pharmacother. 1993 Apr;27(4):480-9. [Pubmed]

• Devineni D, Gallo JM: Zalcitabine. Clinical pharmacokinetics and efficacy. Clin Pharmacokinet. 1995 May;28(5):351-60. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1719

Research Area: Infection
Biological Activity:
Zalcitabine is a nucleoside analog reverse transcriptase inhibitor (NARTI).Zalcitabine is an analog of pyrimidine. It is a derivative of the naturally existing deoxycytidine, made by replacing the hydroxyl group in position 3’ with a hydrogen.It is phosphorylated in T cells and other HIV target cells into its active triphosphate form, ddCTP. This active metabolite works as a substrate for HIV reverse transcriptase, and also by incorporation into the viral DNA, hence terminating the chain elongation due to the missing hydroxyl group. Since zalcitabine is a reverse transcriptase inhibitor it possess activity only against retroviruses. [1]

Sigma Aldrich

308358

Application
Research tool for antiviral (e.g. HIV-1)1 and anticancer studies.2

D5782

Packaging
100, 250, 500 mg in poly bottle
Application
2′,3′-Dideoxycytidine is used as a DNA chain-terminating nucleotide for DNA sequencing methods based on the Sanger chain-termination method.

36775

Biochem/physiol Actions
Infection of NIH Swiss 3T3 cells by 334C murine leukemia virus is inhibited by 50 μM ddCyd without effecting cell growth;1 ddCyd inhibits the in vitro infectivity and cytopathic effects of human Tlymphotropic virus type III/ lymphadenopathy-associated virus (HTLV-III/LAV).2

TRC

Z140000

A pyrimidine nucleoside analogue with antiviral activity.

ChEBI

CHEBI:10101

A pyrimidine 2',3'-dideoxyribonucleoside compound having cytosine as the nucleobase.

Molecule Details

References

PubChem Literature

From Data Sources

• Devineni D, Gallo JM: Zalcitabine. Clinical pharmacokinetics and efficacy. Clin Pharmacokinet. 1995 May;28(5):351-60. Pubmed

• Shelton MJ, O'Donnell AM, Morse GD: Zalcitabine. Ann Pharmacother. 1993 Apr;27(4):480-9. Pubmed

• http://en.wikipedia.org/wiki/Zalcitabine

• van der Vliet, P.C. and Kwant, M.M.: Biochemistry, 20, 2628 (1981)

• Starnes, M.C., and Cheng, Y.: J. Biol. Chem., 262, 988 (1981)

• Mitsuya, H., Broder, S.: Proc. Nat. Acad. Sci. USA, 83, 1911 (1981)

References

Bioactivity

PubChem BioAssay

Bioactivity

Names and Identifiers

Synonyms

IUPAC Traditional name

zalcitabine

Brand Name

HIVID

IUPAC name

4-amino-1-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one

API Name

Zalcitabine

International Nonproprietary Name (INN)

zalcitabine

Molecule Details

DrugBank

DB00943

Drug Groups

approved

Description

Indication

For the treatment of Human immunovirus (HIV) infections in conjunction with other antivirals.

Pharmacology

Toxicity

Affected Organisms

Human Immunodeficiency Virus

Biotransformation

Hepatic

Absorption

Bioavailability is over 80% following oral administration.

Half Life

2 hours

Protein Binding

Less than 4%

Elimination

Distribution

* 0.304 to 0.734 L/kg

Clearance

* 285 mL/min [HIV-infected patients receiving 1.5 mg IV infusion for 1 hour]

References

• Shelton MJ, O'Donnell AM, Morse GD: Zalcitabine. Ann Pharmacother. 1993 Apr;27(4):480-9. [Pubmed]

• Devineni D, Gallo JM: Zalcitabine. Clinical pharmacokinetics and efficacy. Clin Pharmacokinet. 1995 May;28(5):351-60. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1719

Sigma Aldrich

308358

Application
Research tool for antiviral (e.g. HIV-1)1 and anticancer studies.2

D5782

Packaging
100, 250, 500 mg in poly bottle
Application
2′,3′-Dideoxycytidine is used as a DNA chain-terminating nucleotide for DNA sequencing methods based on the Sanger chain-termination method.

36775

TRC

Z140000

A pyrimidine nucleoside analogue with antiviral activity.

ChEBI

CHEBI:10101

A pyrimidine 2',3'-dideoxyribonucleoside compound having cytosine as the nucleobase.

References

PubChem Literature

From Data Sources

• Devineni D, Gallo JM: Zalcitabine. Clinical pharmacokinetics and efficacy. Clin Pharmacokinet. 1995 May;28(5):351-60. Pubmed

• Shelton MJ, O'Donnell AM, Morse GD: Zalcitabine. Ann Pharmacother. 1993 Apr;27(4):480-9. Pubmed