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

• ChemBase ID: 819
• Molecular Formular: C9H13N3O3
• Molecular Mass: 211.21782
• Monoisotopic Mass: 211.09569129
• SMILES: O1[C@@H](n2ccc(nc2=O)N)CC[C@H]1CO
• Canonical SMILES: Nc1ccn(c(=O)n1)[C@H]1CC[C@H](O1)CO
• 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

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-amino-1-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
• IUPAC Traditional name: zalcitabine
• Brand Name: HIVID
• Synonyms: Zalcitabine; 2',3'-Dideoxycytidine; 2’,3’-Dideoxycytidine; Ro 24-2027/000; Dideoxycytidine; DDC; DDCYD; Zalcitabine; Hivid; NSC 606170; 2′,3′-Dideoxycytidine; 2',3'-DIDEOXYCYTIDINE; 2',3'-二脱氧胞啶; 扎西他滨

Database IDs

• CAS Number: 7481-89-2
• MDL Number: MFCD00012188
• Beilstein Number: 654956
• Merck Index: 1410109
• PubChem SID: 46507879; 24862834; 160964282; 24278377
• PubChem CID: 24066

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.673299
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): -1.1882305
• LogD (pH = 7.4): -1.1882266
• Log P: -1.1882265
• Molar Refractivity: 52.2402 cm^3
• Polarizability: 20.097618 Å^3
• Polar Surface Area: 88.15 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -1.29
• LOG S: -1.48
• Solubility (Water): 7.05e+00 g/l

PROPERTIES

Physical Property

• Solubility: 2.42E+004 mg/L; DMSO; Water
• Apperance: White to Off-White Solid
• Melting Point: 201-204°C; 216-220°C; 217-218 °C(lit.)
• Optical Rotation: [α]20/D +75°, c = 0.6 in H2O; +90 (c=0.5 in water)
• Hydrophobicity(logP): -1.3

Safety Information

• Storage Condition: -20°C; Refrigerator
• RTECS: HA3870000
• European Hazard Symbols: X; Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 40; 40-62
• Safety Statements: 22-36; 36/37
• TSCA Listed: 否
• GHS Pictograms: GHS08
• GHS Signal Word: Warning
• GHS Hazard statements: H351; H351-H361
• GHS Precautionary statements: P281; P281-P201-P202-P308+P313-P405-P501A
• Personal Protective Equipment: Eyeshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• Storage Temperature: -20°C; 2-8°C

Product Information

• Purity: ≥98% (HPLC); ≥99.0% (HPLC); 98%; 98+%; 99%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C9H13N3O3

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 - 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.

Sigma Aldrich - 308358

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

Sigma Aldrich - 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

Toronto Research Chemicals - Z140000

A pyrimidine nucleoside analogue with antiviral activity.

REFERENCES

• 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)
• Mitsuya, H., Broder, S.: Proc. Nat. Acad. Sci. USA, 83, 1911 (1981)
• Starnes, M.C., and Cheng, Y.: J. Biol. Chem., 262, 988 (1981)