Fluorescent Tricyclic Analogues of Acyclovir and Ganciclovir. A Structure−Antiviral Activity Study

• Published in: Journal of medicinal chemistry Vol. 44; no. 24; pp. 4284 - 4287
• Main Authors: Golankiewicz, Bozenna, Ostrowski, Tomasz, Goslinski, Tomasz, Januszczyk, Piotr, Zeidler, Joanna, Baranowski, Daniel, de Clercq, Erik
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 22.11.2001; Amer Chemical Soc
• Subjects: Acyclovir - analogs & derivatives; Acyclovir - chemical synthesis; Acyclovir - chemistry; Acyclovir - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Biological and medical sciences; Cell Line; Chemistry, Medicinal; Cytopathogenic Effect, Viral; 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; Life Sciences & Biomedicine; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Structure-Activity Relationship; DERIVATIVES; ACID; Acyclic nucleoside; Angular nitrogen heterocycle; Herpesviridae; Alphaherpesvirinae; Benzene derivatives; Lactam; Tricyclic compound; In vitro; Virus; Position isomer; Structure activity relation; Antiviral; Herpesvirus hominis; Fluorescent compound; Chemical synthesis
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm010922s

Of a series of new guanine base modified 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, evaluated for activity against herpes simplex virus type 1 and 2, several fluorescent analogues, 6-(4-MeOPh)-TACV (8), 7-Me-6-Ph-TACV (17), 6-(4-MeOPh)-TGCV (27), and 7-Me-6-Ph-TGCV (28), were obtained that showed similar potency and selectivity as the parent compounds. The activity was found to be strongly dependent on the nature and steric demands of the substituents in the 6 and/or 7 position.