SynCED: Zalcitabine

Record Information

Version

1.0

Creation Date

2014-09-11 02:06:20 UTC

Update Date

2026-05-14 16:53:39 UTC

Accession Number

CHEM003677

Identification

Common Name

Zalcitabine

Class

Small Molecule

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A dideoxynucleoside compound in which the 3'-hydroxyl group on the sugar moiety has been replaced by a hydrogen.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.

Contaminant Sources

HMDB Contaminants - Urine
IARC Carcinogens Group 2B
STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Amine
Anti-HIV Agent
Antimetabolite
Drug
Ether
Metabolite
Organic Compound
Reverse Transcriptase Inhibitor
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
2',3'-Dideoxycytidine	ChEBI
4-Amino-1-[(2R,5S)-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2(1H)-one	ChEBI
DDC	ChEBI
DDCYD	ChEBI
Dideoxycytidine	ChEBI
Hivid	Kegg
HIVID roche	HMDB
2',3' Dideoxycytidine	HMDB
Hoffman-la roche brand OF zalcitabine	HMDB
Roche brand OF zalcitabine	HMDB
DDC (Antiviral)	HMDB

Chemical Formula

C₉H₁₃N₃O₃

Average Molecular Mass

211.218 g/mol

Monoisotopic Mass

211.096 g/mol

CAS Registry Number

7481-89-2

IUPAC Name

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

Traditional Name

zalcitabine

SMILES

NC1=NC(=O)N(C=C1)[C@H]1CC[C@@H](CO)O1

InChI Identifier

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

InChI Key

WREGKURFCTUGRC-POYBYMJQSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as pyrimidine 2',3'-dideoxyribonucleosides. Pyrimidine 2',3'-dideoxyribonucleosides are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at positions 2 and 3.

Kingdom

Organic compounds

Super Class

Nucleosides, nucleotides, and analogues

Class

Pyrimidine nucleosides

Sub Class

Pyrimidine 2',3'-dideoxyribonucleosides

Direct Parent

Pyrimidine 2',3'-dideoxyribonucleosides

Alternative Parents

Substituents

Pyrimidine 2',3'-dideoxyribonucleoside
Aminopyrimidine
Pyrimidone
Hydropyrimidine
Pyrimidine
Imidolactam
Heteroaromatic compound
Tetrahydrofuran
Oxacycle
Azacycle
Organoheterocyclic compound
Hydrocarbon derivative
Organic oxide
Organopnictogen compound
Primary amine
Primary alcohol
Organooxygen compound
Organonitrogen compound
Organic oxygen compound
Alcohol
Amine
Organic nitrogen compound
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

pyrimidine 2',3'-dideoxyribonucleoside (CHEBI:10101 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	217 - 218°C
Boiling Point	Not Available
Solubility	7.05e+00 g/L

Predicted Properties

Property	Value	Source
Water Solubility	7.05 g/L	ALOGPS
logP	-1.3	ALOGPS
logP	-1.2	ChemAxon
logS	-1.5	ALOGPS
pKa (Strongest Acidic)	14.67	ChemAxon
pKa (Strongest Basic)	0.18	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	88.15 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	52.24 m³·mol⁻¹	ChemAxon
Polarizability	20.86 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Toxicity Profile

Route of Exposure

Bioavailability is over 80% following oral administration.

Mechanism of Toxicity

Zalcitabine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Within cells, zalcitabine is converted to its active metabolite, dideoxycytidine 5'-triphosphate (ddCTP), by the sequential action of cellular enzymes. ddCTP interferes with viral RNA-directed DNA polymerase (reverse transcriptase) by competing for utilization of the natural substrate deoxycytidine 5'-triphosphate (dCTP), as well as incorpating into viral DNA. Due to it's lack of a 3'-OH group, the formation of a 5' to 3' phosphodiester linkage that is necessary for DNA chain elongation is inhibited, thus leading to the termination of viral DNA growth.

Metabolism

Hepatic. Route of 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. Half Life: 2 hours

Toxicity Values

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 1.5 weeks of treatment subsequent to the development of a rash and fever.

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

2B, possibly carcinogenic to humans. (3)

Uses/Sources

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

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available