Abstract
In search of strongly fluorescent tricyclic analogues of acyclovir (ACV, 1) and ganciclovir (GCV, 2), derivatives of the 3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purine system, several 6-[4-(acyloxy)phenyl], 6-[4-(acylamino)phenyl], and 6-[4-(phenoxycarbonyloxy)phenyl]-substituted TACV and TGCV analogues were synthesized and evaluated for their activity against herpes simplex virus types 1 and 2 in cell culture. All TACV and TGCV analogues showed strong fluorescence (quantum yield of 30-65% vs 2-aminopurine 100%). The 6-[4-(phenoxycarbonyloxy)phenyl]-substituted compounds 11 and 19 displayed the best combination of the fluorescence and antiviral potency.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acyclovir / analogs & derivatives*
-
Acyclovir / chemical synthesis*
-
Acyclovir / chemistry
-
Acyclovir / pharmacology
-
Antiviral Agents / chemical synthesis*
-
Antiviral Agents / chemistry
-
Antiviral Agents / pharmacology
-
Cell Culture Techniques
-
Fluorescent Dyes / chemical synthesis*
-
Fluorescent Dyes / chemistry
-
Fluorescent Dyes / pharmacology
-
Ganciclovir / analogs & derivatives
-
Ganciclovir / chemical synthesis
-
Ganciclovir / chemistry
-
Ganciclovir / pharmacology
-
Herpesvirus 1, Human / drug effects
-
Herpesvirus 2, Human / drug effects
-
Heterocyclic Compounds, 3-Ring / chemical synthesis*
-
Heterocyclic Compounds, 3-Ring / chemistry
-
Heterocyclic Compounds, 3-Ring / pharmacology
-
Humans
-
Purines / chemical synthesis*
-
Purines / chemistry
-
Purines / pharmacology
-
Structure-Activity Relationship
Substances
-
3,9-dihydro-3-((1,3-dihydroxy-2-propoxy)methyl)-9-oxo-6-(4-(phenoxycarbonyloxy)phenyl)-5H-imidazo(1,2-a)purine
-
3,9-dihydro-3-((2-hydroxyethoxy)methyl)-9-oxo-6-(4-(phenoxycarbonyloxy)phenyl)-5H-imidazo(1,2-a)purine
-
Antiviral Agents
-
Fluorescent Dyes
-
Heterocyclic Compounds, 3-Ring
-
Purines
-
Ganciclovir
-
Acyclovir