Triacetylganciclovir
[CAS# 86357-14-4]

Identification

• Classification: API >> Synthetic anti-infective drugs >> Antiviral drugs
• Name: Triacetylganciclovir
• Synonyms: N-[9-[[2-(Acetyloxy)-1-[(acetyloxy)methyl]ethoxy]methyl]-6,9-dihydro-6-oxo-1H-purin-2-yl]acetamide
• Molecular Formula: C₁₅H₁₉N₅O₇
• Molecular Weight: 381.34
• CAS Registry Number: 86357-14-4
• EC Number: 617-838-3
• SMILES: CC(=O)NC1=NC2=C(C(=O)N1)N=CN2COC(COC(=O)C)COC(=O)C

Properties

• Density: 1.5±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.629, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS08 Danger
• Hazard Statements: H340-H341-H351-H360-H361-H361fd-H362
• Precautionary 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.	2	H361
Reproductive toxicity	Lact.	-	H362
Reproductive toxicity	Repr.	1A	H360
Germ cell mutagenicity	Muta.	2	H341
Germ cell mutagenicity	Muta.	1B	H340

Discovory and Applicatios

Triacetylganciclovir is an acetylated derivative of ganciclovir, designed to improve the bioavailability of the parent drug. It is a prodrug of ganciclovir, meaning that it is converted into the active form of the drug within the body after administration. Triacetylganciclovir has enhanced lipophilicity, which allows for better absorption in the gastrointestinal tract, and it is converted into ganciclovir primarily through the action of esterases, enzymes that cleave the acetyl groups, during metabolism.

The primary use of triacetylganciclovir is as a treatment for infections caused by cytomegalovirus (CMV), particularly in patients with weakened immune systems, such as those with HIV/AIDS, organ transplant recipients, or patients undergoing chemotherapy. It acts in the same way as ganciclovir by inhibiting viral DNA polymerase, which prevents viral replication. However, due to its improved absorption, triacetylganciclovir can be taken orally, which is a significant advantage over ganciclovir, which typically requires intravenous administration.

Once triacetylganciclovir enters the body, it is hydrolyzed by esterases into ganciclovir. The released ganciclovir is then active and works by inhibiting the viral DNA polymerase enzyme, disrupting the replication of the CMV virus and preventing further spread of the infection. The antiviral action is similar to that of ganciclovir, which is known for its effectiveness in treating CMV retinitis, CMV-induced colitis, and CMV pneumonia, among other CMV-related complications.

Triacetylganciclovir’s main advantage lies in its improved pharmacokinetics, particularly its ability to be administered orally. This feature makes it more convenient for patients who need long-term therapy for CMV infections, compared to ganciclovir, which requires hospitalization and intravenous infusion for administration. The oral route also improves patient compliance, especially in cases where long-term antiviral therapy is needed, such as for the prevention of CMV reactivation in organ transplant patients.

In terms of safety and side effects, triacetylganciclovir is similar to ganciclovir. Common adverse effects include hematological toxicity, such as neutropenia (low white blood cell count) and thrombocytopenia (low platelet count). Other side effects may include gastrointestinal issues, liver enzyme abnormalities, and kidney dysfunction. As with ganciclovir, close monitoring of blood counts and renal function is required during treatment.

Resistance to triacetylganciclovir can develop in a manner similar to ganciclovir, particularly in patients who have been on long-term treatment. Resistance is typically due to mutations in the CMV thymidine kinase or DNA polymerase genes, which can result in a reduced effectiveness of the drug.

Triacetylganciclovir is also used as part of a treatment strategy for CMV prophylaxis in immunocompromised patients, particularly in those undergoing organ transplants. It is often preferred over ganciclovir in cases where long-term oral therapy is needed due to its improved bioavailability and ease of use.

In summary, triacetylganciclovir is an oral prodrug of ganciclovir that offers the advantage of improved absorption compared to ganciclovir. It is primarily used in the treatment and prevention of CMV infections in immunocompromised patients. While it is effective in treating CMV-related diseases, its use is limited by potential side effects, particularly hematological toxicity. It is generally well tolerated and serves as an important option for patients requiring long-term antiviral therapy for CMV infections.

References

1976. Chemical manipulation of the heat resistance of Clostridium botulinum spores. Applied and Environmental Microbiology, 31(4).
DOI: 10.1128/aem.31.4.492-498.1976

2004. By Transpurination. Science of Synthesis.