Synthesis and antiviral activity of novel N-substituted derivatives of acyclovir.
Novel N-substituted derivatives of acyclovir (1a) were synthesized and evaluated for their antiviral, antimetabolic, and antitumor cell properties in vitro. Monomethylation of 1a at positions 1, 7, and N-2 gave compounds 2-4, respectively. When positions 1 and N-2 were linked together by an isopropeno group, the tricyclic 9-[(2-hydroxyethoxy)methyl]-1,N-2-isopropenoguanine (5) was obtained. Compound 5 was then further methylated at positions N-2 and 7 to give 6 and 7, respectively. None of the new acyclovir derivatives showed any appreciable antimetabolic or antitumor cell activity. However, compounds 2 and 5 exhibited a marked antiherpetic activity. Their activity spectrum was similar to that of acyclovir, and their selectivity as inhibitors of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was at least as great as, if not greater than, that of acyclovir.
Boryski
J
J
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan.
Golankiewicz
B
B
De Clercq
E
E
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000138:chemical synthesis; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D008745:Methylation; D051379:Mice; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D018139:Simplexvirus / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000473:pathology; D014779:Virus Replication / Q000187:drug effects
D000963:Antimetabolites; D012313:RNA; D004247:DNA; D000212:Acyclovir