Zalcitabine, 扎西他滨

2',3'-Dideoxycytidine

Zalcitabine is an analog of pyrimidine derived from deoxycytidine with the replacement of the hydroxyl group in position 3’ with a hydrogen. In cells, it is phosphorylated to the active triphosphate form, ddCTP, which acts as a substrate for HIV reverse transcriptase (Ki = 51 nM). It incorporates into viral DNA where it terminates chain elongation when the missing hydroxyl group is encountered. Zalcitabine was the third antiretroviral approved by the FDA for treatment of HIV infection and AIDS.

A pyrimidine nucleoside analogue with antiviral activity.

Pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards

Zalcitabine is a synthetic dideoxynucleoside. After intracellular phosphorylation to its active metabolite, zalcitabine preferentially inhibits the gamma form of DNA polymerase present in tumor cell mitochondria, resulting in the inhibition of tumor cell mitochondrial DNA replication and tumor cell death. (NCI04)

Zalcitabine, also known as DDC or hivid, 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. Zalcitabine is a drug which is used for the treatment of human immunovirus (hiv) infections in conjunction with other antivirals. Zalcitabine exists as a solid, slightly soluble (in water), and a very weakly acidic compound (based on its pKa). Zalcitabine has been detected in multiple biofluids, such as urine and blood. Within the cell, zalcitabine is primarily located in the cytoplasm. In humans, zalcitabine is involved in the zalcitabine action pathway. Zalcitabine is formally rated as a possible carcinogen (by IARC 2B) and is also a potentially toxic compound.

Zalcitabine is a pyrimidine 2',3'-dideoxyribonucleoside compound having cytosine as the nucleobase. It has a role as an antiviral drug, an antimetabolite and a HIV-1 reverse transcriptase inhibitor.

Title: Zalcitabine

CAS Registry Number: 7481-89-2

CAS Name: 2',3'-Dideoxycytidine

Additional Names: dideoxycytidine; ddCyd

Trademarks: Hivid (Roche)

Molecular Formula: C9H13N3O3

Molecular Weight: 211.22

Percent Composition: C 51.18%, H 6.20%, N 19.89%, O 22.72%

Literature References: Pyrimidine nucleoside analog with antiviral activity. Prepn: J. P. Horwitz et al., J. Org. Chem. 32, 817 (1967); R. Marumoto, M. Honjo, Chem. Pharm. Bull. 22, 128 (1974). Prepn and structure-activity study: T.-S. Lin et al., J. Med. Chem. 30, 440 (1987). In vitro inhibition of viral DNA synthesis: P. C. van der Vliet, M. M. Kwant, Biochemistry 20, 2628 (1981); of HIV-1 virus replication: H. Mitsuya, S. Broder, Proc. Natl. Acad. Sci. USA 83, 1911 (1986). Phosphorylation by human cells: D. A. Cooney et al., Biochem. Pharmacol. 35, 2065 (1986). Metabolism by human cells: M. C. Starnes, Y. Cheng, J. Biol. Chem. 262, 988 (1987). Potential application in acquired immunodeficiency syndrome (AIDS): E. De Clercq, J. Med. Chem. 29, 1561 (1986).

Properties: Crystals from ethanol + benzene, mp 215-217° (Horwitz); also reported as mp 209-210° (Lin). [a]D25 +81° (c = 0.635 in water). uv max in 0.1N HCl: 280 nm (e 17720); in 0.1N NaOH: 270 nm (e 8410).

Melting point: mp 215-217° (Horwitz); mp 209-210° (Lin)

Optical Rotation: [a]D25 +81° (c = 0.635 in water)

Absorption maximum: uv max in 0.1N HCl: 280 nm (e 17720); in 0.1N NaOH: 270 nm (e 8410)

Therap-Cat: Antiviral.

Keywords: Antiviral; Purines/Pyrimidinones; Reverse Transcriptase Inhibitor.