Synthesis and biological activity of strongly fluorescent tricyclic analogues of acyclovir and ganciclovir.
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.
Goslinski
Tomasz
T
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
Golankiewicz
Bozenna
B
De Clercq
Erik
E
Balzarini
Jan
J
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018929:Cell Culture Techniques; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
C468793:3,9-dihydro-3-((1,3-dihydroxy-2-propoxy)methyl)-9-oxo-6-(4-(phenoxycarbonyloxy)phenyl)-5H-imidazo(1,2-a)purine; C468792:3,9-dihydro-3-((2-hydroxyethoxy)methyl)-9-oxo-6-(4-(phenoxycarbonyloxy)phenyl)-5H-imidazo(1,2-a)purine; D000998:Antiviral Agents; D005456:Fluorescent Dyes; D006575:Heterocyclic Compounds, 3-Ring; D011687:Purines; D015774:Ganciclovir; D000212:Acyclovir