Tricyclic nucleoside analogues as antiherpes agents

• Published in: Antiviral research Vol. 71; no. 2; pp. 134 - 140
• Main Authors: Golankiewicz, Bozenna, Ostrowski, Tomasz
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.09.2006; Elsevier
• Subjects: Acyclovir; Acyclovir - analogs & derivatives; Acyclovir - chemistry; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Antivirals; Biological and medical sciences; Fluorescence; Ganciclovir; Ganciclovir - analogs & derivatives; Ganciclovir - chemistry; Herpes simplex viruses; Herpesviridae - classification; Herpesviridae - drug effects; Herpesviridae Infections - virology; Human viral diseases; Humans; Infectious diseases; Medical sciences; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Tricyclic analogues; Viral diseases; Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye; Fluorescence; Ganciclovir; Tricyclic analogues; Acyclovir; Herpes simplex viruses; Antivirals; Acyclic nucleoside; Purine nucleoside; Herpes; Tricyclic compound; Infection; Viral disease; Aciclovir; Nucleoside analog; Antiviral
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2006.05.004

Tricyclic (T) guanine analogues are a class of compounds in which the N1 and N 2 atoms of the guanine system are linked by etheno bridge to form the 3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purine system. Almost 70 tricyclic derivatives of guanine-type potent antiherpetic agents acyclovir (ACV), ganciclovir (GCV) and 9-{[cis-1′,2′-bis(hydroxymethyl)cycloprop-1′-yl]methyl}guanine were synthesized and evaluated for activity against viruses of the herpes family. Here, we review the most successful compounds in terms of their antiviral activity and physico-chemical properties. These features are modulated by the kind and position of additional substituents present in the appended third ring of aglycone. The best antiherpetic activity–fluorescence combinations as well as activity of compounds in comparison to parent congeners are summarized. The data presented indicate that compounds of the 6-(4-RPh) family are of particular importance because of their advantageous antiviral potency, increased lipophilicity and good or moderate fluorescence properties.