As it is evident from the chemical structure, acyclovir looks like a nucleoside analog of guanosine in side chain of which, instead of the traditional cyclic sugar residue a 2-hydrox-yethoxymethyl acyclic side chain is present. Acyclovir possesses antiviral activity with respect to types 1 and 2 of herpes simplex, shingles virus, Epstein-Barr virus, and cytomegalovirus.
The mechanism of antiviral activity consists of its transformation to triphosphate and subsequent inhibition of viral DNA synthesis. Its action is highly selective. Acyclovir diffuses into the cell infected by a virus and phosphorylates thymidine kinase of herpes simplex to a monophosphate. Uninfected cells do not use acyclovir as a substrate. The monophosphate is subsequently transformed to a diphosphate, and then a triphosphate, which inhibits viral DNA polymerase, as well as viral DNA, where it acts in the process of breaking the chain, thus preventing further elongation of the DNA chains and correspondingly, replication of the DNA virus. Acyclovir is used for herpes simplex that has attacked the eyes and genetilia, for herpes in other locations, shingles, and chicken pox. Synonyms of this drug are aovirax, cycloviran, sifiviral, and others.
Vidarabine: Vidarabine, 9-5-arabinofuranosyl-6-amino-9-H-pyrine (36.1.10), is synthesized both microbiologically from the culture fluid of the actinomycete Streptomyces antibioticus NRRL 3238, as well as synthetically. It is synthesized from the acetonide-^-D-xylofuranoside of adenine—9-(3',5'-0-isopropyliden-/i-D-xylofuranoside)adenine, which is reacted with methanesulfonyl chloride to make the mesylate 9-(3',5'-0-isopropyliden-2'-0-methansul-fonyl-/i-D-xydlofuranoside)adenine (36.1.7). Prolonged heating in 90% acetic acid removes the acetonyl protective group from the resulting compound, giving the product (36.1.8).
Reacting this with sodium methoxide leads to the formation of an epoxide— 9-(2',3'-anhydro-/i-luxofuranosyl)adenine (36.1.9). Finally, heating this epoxide with sodium acetate or benzoate opens the epoxide ring in the dimethylformamide-water system to make the corresponding dihydroxy derivative, vidarabine [12,13].
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