Ganciclovir mono-O-acetate
[CAS# 88110-89-8]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Ketones
• Name: Ganciclovir mono-O-acetate
• Synonyms: 9-[[2-(Acetyloxy)-1-(hydroxymethyl)ethoxy]methyl]-2-amino-1,9-dihydro-6H-purin-6-one
• Molecular Formula: C₁₁H₁₅N₅O₅
• Molecular Weight: 297.27
• CAS Registry Number: 88110-89-8
• EC Number: 680-297-7
• SMILES: CC(=O)OCC(CO)OCN1C=NC2=C1N=C(NC2=O)N

Properties

• Density: 1.7±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.692, Calc.^*

Safety Data

• Hazard Symbols: GHS08 Danger
• Risk Statements: H341-H350-H361-H362
• Safety Statements: P203-P260-P263-P264-P270-P280-P318-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Carcinogenicity	Carc.	2	H351
Reproductive toxicity	Repr.	1A	H360
Reproductive toxicity	Repr.	2	H361
Germ cell mutagenicity	Muta.	1B	H340
Germ cell mutagenicity	Muta.	2	H341
Reproductive toxicity	Lact.	-	H362

Discovery and Applications

Ganciclovir mono-O-acetate is an acetylated derivative of ganciclovir, a potent antiviral agent primarily used for the treatment of cytomegalovirus (CMV) infections, particularly in immunocompromised patients. The acetylation of the hydroxyl group in ganciclovir results in the formation of this prodrug, which is designed to improve the pharmacokinetics of the parent compound, particularly its absorption and bioavailability.

The primary function of ganciclovir mono-O-acetate is to act as a prodrug of ganciclovir. When administered, it undergoes hydrolysis in the body, typically through the action of esterases, which cleave the acetate group and convert it back to the active ganciclovir molecule. Ganciclovir itself is an acyclic nucleoside analogue of guanosine, and it works by inhibiting viral DNA polymerase, thereby preventing viral DNA replication. This mechanism is effective against a wide range of herpesviruses, including CMV, which is a key target for ganciclovir therapy.

The acetylation of ganciclovir into its mono-O-acetate form offers several potential advantages. One of the primary benefits is the improvement of the drug's solubility and permeability, which can facilitate better absorption when taken orally. Since ganciclovir itself has limited bioavailability when administered orally, the prodrug form, ganciclovir mono-O-acetate, is expected to enhance its oral absorption, potentially allowing for more convenient oral dosing compared to the intravenous administration of ganciclovir. Once in the body, the prodrug is hydrolyzed into the active drug, restoring its antiviral effects.

However, despite these advantages, the use of ganciclovir and its derivatives, including ganciclovir mono-O-acetate, is associated with certain limitations and potential side effects. The primary side effects of ganciclovir, whether in its parent form or as a prodrug, include hematological toxicity, such as neutropenia (low white blood cell count), thrombocytopenia (low platelet count), and anemia. Other potential adverse effects include gastrointestinal symptoms, liver enzyme abnormalities, and renal toxicity. Close monitoring of patients' blood counts and renal function is necessary during treatment.

Ganciclovir mono-O-acetate, like other prodrugs, is designed to improve the pharmacokinetics of the parent compound, but it is primarily intended for use in situations where ganciclovir's effectiveness is needed for treating CMV infections, especially in patients with compromised immune systems. These patients, such as those undergoing organ transplants or those with HIV/AIDS, are at increased risk of CMV reactivation, and antiviral treatment is essential to manage and prevent serious complications from the virus.

In addition to its role in CMV infections, ganciclovir and its derivatives have been explored for their potential to treat other viral infections, though their use outside of CMV is less widespread. The prodrug form of ganciclovir may offer more options in terms of administration routes and patient compliance, particularly in settings where long-term treatment is required.

In summary, ganciclovir mono-O-acetate is an acetylated prodrug of ganciclovir designed to improve the drug's pharmacokinetics, particularly its oral bioavailability. Once administered, it is converted into active ganciclovir, which exerts its antiviral effects by inhibiting viral DNA replication. While it is primarily used for the treatment of CMV infections in immunocompromised patients, its use is limited by the potential for hematological toxicity and other side effects. The prodrug form offers an alternative route of administration that may improve patient compliance, particularly for long-term antiviral therapy.

References

2002. Effect of Mono- and Di-acylation on the Ocular Disposition of Ganciclovir: Physicochemical Properties, Ocular Bioreversion, and Antiviral Activity of Short Chain Ester Prodrugs. Journal of Pharmaceutical Sciences, 91(3).
DOI: 10.1002/jps.10072