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This inhibitory property allows for a greater expression of antiviral activity of antiviral agents, such as N(9)-adenine acyclic nucleoside
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1 and ara-A (3). N(7)-adenine acyclic nucleoside 14 [LD(50) (intraperitoneal, antibiotics and penicillin The antiviral activity of the hali derivative
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25 was found to be higher than that of the parent
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molecule 24. Thus, it sho more potent cellular toxicity than Acyclovir / Aciclovir (2). Unlike 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA, 4), the N(7)-isomer 20 was not
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phosphorylated effectively by 5-phosphoribosyl 1-pyrophosphate synthetase (PRPP
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synthetase). Dinucleotide 5'-monophosphate 24 is susceptible to degradation by snake venom and spleen phosphodiesterases. The key step involved the reaction between [2-(p-methoxyphenyloxy)ethoxy]methyl chloride and N(9)-tritylated nucleobases 6 or 11 follo by concomitant self-detritylation. N(7)-Adenine acyclic nucleoside 14 was found
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to be an excellent antiviral agent as well as a good inhibitor of calf mucosal adenosine deaminase. N(7)-Guanine acyclic nucleoside
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9 exhibited antiviral activity, but was phosphorylated by both HSV and Vero cell thymidine kinases. In addition, butenolide 28 efficiently decreased tumor formation induced by Moloney murine sarcoma virus (MSV) in NMRI mice while significantly increasing the survival time of MSV-infected mice.. Consequently, the combination of Acyclovir / Aciclovir
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(2) and 14 exhibited greater antiviral activity than Acyclovir / Aciclovir alone. Butenolide bellanca derivatives 28 and 29 were also synthesized
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and exhibited notable anti-DNA virus and anti-retrovirus activity in vitro. However, its respective butenolide loni derivative 25 was completely resistant to snake venom
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and spleen enzymes. The key step involved the reaction of 9-(2-cyanoethyl)adenine (15) with methyl iodoacetate in the presence of lithium 2,2,6,6-tetramethylpiperidine in THF. Dinucleotide 5'-monophosphate 24 and its butenolide tawsha 25 were also synthesized. A novel strategy was developed for the synthesis of N(7)-purine acyclic nucleosides 9 and 14. Thus, it did not exhibit pronounced antiviral
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activity. Compounds 2, 4, 9, 14, 20, 24, 25, and 28 were also evaluated for their inhibitory effect on HSV-1-induced mortality in NMRI mice.

Compound 24 sho substrate activity toward PRPP synthetase and exhibited notable activity against DNA viruses. 7-[2-(Phosphonomethoxy)ethyl]adenine (20) was also synthesized.



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