Herpes virus antiviral agents

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). 

Lemon balm isa perennial herb with heart-shaped leaves that has been used for hundreds of years. Its scientific name is Melissa officinalis. Traditionally the herb has been used for Graves disease (see Chap. 51), asa sedative, arrtispasmodic, and an antiviral agent. When used topically, lemon balm has antiviral activity against herpes simplex virus(HSM). No adverse reactions have been reported when lemon balm is used topically. 

In this chapter, we have described the spectrum of antiviral activities that have been discovered beyond the world of nucleoside analogues, protease and fusion inhibitors. The compounds and mechanisms described here may one day add significantly to the armamentarium of antiviral agents, not only against Herpes Simplex, Hepatitis B and Human Immunodeficiency Virus, but also against Hepatitis C and Human Cytomegalovirus. 

Alkoxyalkanoate esters have been used as prodrugs to improve the oral bioavailability of antiviral agents such as (+)-cyclaradine (carbocyclic arabino-furanosyl adenine) [41]. (+)-Cyclaradine has been shown to be effective against herpes simplex virus in tissue culture at noncytotoxic concentrations. Two prodrugs of (+)-cyclaradine, namely, (+)-cyclaradine-5 -methoxyacetate (CM) and (+)-cyclaradine-5,-ethoxypropionate (CE) (Fig. 2), may be promising candidates... 

A -(4-Chlorobenzyl)-7-substituted-4-oxo-477-pyrimido[l,2- ]pyridazine-3-carboxamides have been claimed as compounds to treat atherosclerosis and restenosis <2004W02004/019933> and as antiviral agents, particularly against herpes viruses <2002W02002/004444>. The 7-substituted-2-phenyl-pyrimido[l,2- ]pyridazin-5-ium-3-olates 99... 

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. 

Pharmacology Penciclovir is an antiviral agent active against herpes viruses. It has in vitro inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). 

The specific antiviral agents used to treat cutaneous infections caused by herpes simplex and varicella zoster viruses are discussed in Chapter 50. 

Idoxuridine (9.7) and trifluridine (9.8) are antiviral agents that are phosphorylated to their active form in virus-infected cells, and thus show specificity for two reasons their higher affinity for the viral enzyme, and the higher phosphorylase levels in viral-infected than in normal cells. Both compounds have been used locally on lesions of HSV-1 and HSV-2 (the latter of which causes genital herpes, now reaching epidemic proportions) with fair success. They are rather toxic if administered parenterally, as are all moderately selective antimetabolities. 

Most bacterial infections can be treated successfully with antibiotics, but the development of satisfactory antiviral agents has been slow. Yet we are susceptible to many dangerous virus diseases, and viruses also take a huge toll among domestic animals and plants.3 The first antiviral drug, 5-iodo-2 -deoxyuridine (idoxuridine), was introduced in 1962 and was used for 20 years by ophthalmologists to treat serious eye infections by the herpes simplex virus (HSV). 

Development of new, more selective antiviral agents related to io5dU and br5dU have produced promising new candidates, including, for example, ( )-5-bromo- and (E)-5-iodovinyldeoxyuridine (BVdU and IVdU) (87). Both BVdU and IVdU are effective in the treatment of varicella-zoster virus (VZV), responsible for shingles, and herpes simplex virus 1 (HSV-1)127. 

Clove is a potent antiviral agent and eugenin isolated from clove buds showed antiviral activity against Herpes simplex virus at a concentration of lOpg/ml (Kim et al., 2001 Chaieb et al., 2007). 

Although oral corticosteroids have had an established use in herpes zoster treatment, their value has become controversial.They are clearly contraindicated in HIV and while the virus is still present in immunocompetent patients. Some authors report increased quality of life and decreased acute pain with oral steroid use in the elderly, but this value is offset by potential risk. Significant relief may be obtained with early antiviral therapy so that oral steroids are an unnecessary risk. Oral steroids are of no value in preventing PHN as was previously believed. The duration of PHN, however, is significantly shortened by early and aggressive use of oral antiviral agents in the acute phase of herpes zoster. Tricyclic antidepressants may also be useful when prescribed at the time of acute... 

Phosphonoformate (22) (Fig. 17.17) is an antiviral agent that is used clinically in the treatment of herpes simplex virus (HSV) and human cytomegalovirus (HCMV) (91). It acts as a product analog, blocking the pyrophosphate-binding site, in the reaction catalyzed by DNA polymerase (Equation 17.35). It is also effective, using the same mechanism, against HIV reverse transcriptase (91). 

Hitchcock MJM, Jaffe HS, Martin JC, Stagg RJ. Cidofovir, a new agent with potent anti-herpes virus activity. Antiviral Chem Chemother 1996 7 115-127. 

Which of the antiviral agents are active against herpes simplex virus (HSV) ... 

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