Document Report Card

ID: ALA1122925

Journal: J Med Chem

Title: Modifications on the heterocyclic base of acyclovir: syntheses and antiviral properties.

Authors: Beauchamp LM, Dolmatch BL, Schaeffer HJ, Collins P, Bauer DJ, Keller PM, Fyfe JA.

Abstract: A group of compounds was prepared in which variations of the ring portion of the acyclovir (ACV) structure were made. These modifications included monocyclic (isocytosine, triazole, imidazole), bicyclic (8-azapurine, pyrrolo[2,3-d]pyrimidine, pyrazolo[3,4-d]pyrimidine) and tricyclic (linear benzoguanine) congeners. The derivatives were evaluated against herpes simplex virus type 1 (HSV-1) by the plaque-inhibition and plaque-reduction methods with only the 8-azapurine analogue 28 showing some activity. In a test measuring the ability of these compounds to inhibit the HSV-1 thymidine kinase, 28 and the tricyclic derivative 38 exhibited competition with ACV for binding to the enzyme. The inability of the group to exert significant antiherpetic action is attributed to their lack of phosphorylation to the requisite triphosphate stage.

CiteXplore: 2991522

DOI: 10.1021/jm00146a002