Synthesis and antiviral activity of novel N-substituted derivatives of acyclovir
- 1 July 1988
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 31 (7) , 1351-1355
- https://doi.org/10.1021/jm00402a017
Abstract
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.This publication has 22 references indexed in Scilit:
- A new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxyl]methyl]guanine, highly active in vitro against herpes simplex virus types 1 and 2Antimicrobial Agents and Chemotherapy, 1982
- Inhibition of purified human and herpes simplex virus-induced DNA polymerases by 9-(2-hydroxyethoxymethyl)guanine triphosphate. Effects on primer-template function.Journal of Biological Chemistry, 1981
- Enzymatic phosphorylation of acyclic nucleoside analogs and correlations with antiherpetic activitiesBiochemical Pharmacology, 1981
- Phosphorylation of acyclovir (acycloguanosine) monophosphate by GMP kinase.Journal of Biological Chemistry, 1980
- Inhibition by acyclovir of cell growth and DNA synthesis of cells biochemically transformed with Herpesvirus genetic informationVirology, 1980
- Inhibition of herpes simplex virus-induced DNA polymerase activity and viral DNA replication by 9-(2-hydroxyethoxymethyl)guanine and its triphosphateJournal of Virology, 1979
- Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl)guanine.Journal of Biological Chemistry, 1978
- 9-(2-Hydroxyethoxymethyl)guanine activity against viruses of the herpes groupNature, 1978
- Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanineProceedings of the National Academy of Sciences, 1977
- Purine Nucleosides. VI. Further Methylation Studies of Naturally Occurring Purine Nucleosides*Biochemistry, 1964