Antiviral agents acyclovir

Novel isosteres 545 of the antiviral agent acyclovir were synthesized in three stages (84JHC697) by dehydrative coupling of 3-amino-6-aminomethyl[ 1,2,4]triazin-5-(4//)-one with 2-(benzoyloxy)ethoxyacetic acid to give the respective amide that cyclized and deprotected to give 545. It showed no activity against herpes simplex virus types I and II in cell culture (Scheme 112). 

Antiviral agents acyclovir, amantadine, azidofhymidine Diuretics furosemide, hydrochlorothiazide, efhacrynic acid ACE inhibitors captopril, enalapril, ramipril, delapril, quinapril Antineoplastics methotrexate, azathioprine, doxorubicin, 5-fluouracil Antiepileptics valproic acid (from Ref. [95])... 

The C-analog 549 of the potent antiviral agent acyclovir [9-(2-hydroxye-thoxymethyl)guanine (ACV)] was prepared by cyclizing the imidazol-2-yl acyclo C-nucleoside 547 with benzoylisothiocyanate as shown in Scheme 146 (83JHC1169). 

Figure 9.15 An example of the use of a prodrug to improve carrier-mediated transport. Valacyclovir, an L-valine ester prodrug, is transported across intestinal epithelial cell membranes by the HPTl and PEPTl transporters, and is then enzymatically hydrolyzed to the antiviral agent acyclovir before being converted to the true active component, acyclovir triphosphate, in cells.

Organotin Oligomeric Drugs Containing the Antiviral Agent Acyclovir... 

Aciclovir (acyclovir) was one of the first effective selective antiviral agents. It is a guanine derivative of value in treating herpes viruses, though it does not eradicate them, and is only useful if drug treatment is started at the onset of infection. 

In HSV and VZV, the most common mechanism of resistance to acyclovir involves mutations that result in decreased thymidine kinase activity. Therefore, these viral mutants exhibit cross-resistance to other antiviral agents that require thymidine kinase activation, such... 

Detailed pharmacology of acyclovir, valacyclovir, penciclovir and famciclovir is discussed in detail in chapter Chemotherapeutic agents- Antiviral agents. ... 

Mechanism of Action. Foscarnet works somewhat like acyclovir and ganciclovir that is, foscarnet inhibits the DNA polymerase enzyme necessary for viral DNA replication. Foscarnet differs from these other antiviral drugs, however, in that it does not require phosphorylation (activation) by enzymes such as viral thymidine kinase. Certain strains of viruses are thymidine-kinase deficient, meaning that these viruses lack the enzyme needed to activate antiviral agents... 

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