title: Synthesis and biological activity of strongly fluorescent tricyclic analogues of acyclovir and ganciclovir.
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.
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Goslinski
authors.forename: Bozenna
authors.initials: B
authors.lastname: Golankiewicz
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
mesh_terms: 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
chemical_list: 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