Antiherpetic drug

The potent antiherpetic drug 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir, Zovirax) (78NAT583) possesses potent antiviral activity in cells infected with herpes simplex virus type 1 (HSV-1), but it is essentially nontoxic to uninfected host cells. The discovery of acyclovir (ACV) has... 

Deres K, Schroder CH, Paessens A, Goldmann S, Hacker HJ, Weber O, Kramer T, Niewohner U, Pleiss U, Stoltefuss J et al. (2003) Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science 299 893-896 Ehon GB, Furman PA, Fyfe JA, de Miranda P, Beauchamp L, Schaeffer HJ (1977) Selectivity of action of an antiherpetic agent, 9-(2-hydroxy ethoxy methyl) guanine, Proc Natl Acad Sci USA 74 5716-5720... 

Idoxuridine, which is active against Herpes simplex and Varicella zoster, has only been used in topical antiherpetic solutions. Idoxuridine has been used to treat superficial keratitis, but with poor results in deep stromal diseases because of poor solubility. However, idoxuridine is unstable and cannot eliminate the virus from the eye. Drug allergy and toxicity occur in 5-8% of patients. 

The synthesis and biological activity of the new acyclic heterodinucleotide (113) that consists of both an antiherpetic (acyclovir) and an antiretroviral (2-(phosphonomethoxy)propyl-adenine) drug linked by a pyrophosphate bridge were reported. The heterodinucleotide (113), prepared from the reaction of a morpholidate derivative of PMPA and the tributylammonium salt of acyclovir monophosphate in the presence of pyridine, behaved as a pro-drug in macrophages. Anti-HIV and anti-HSV activity of this compound were demonstrated in HIV-lfia-L and HSV-1-infected macrophages. ... 

Acyclovir Wellcome lactam antibiotics) DNA polymerase inhibitor (antiherpetic) 1975 1974 Breakthrough drug Breakthrough drug... 

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