Tricyclic nucleoside analogues as antiherpes agents.
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.
Golankiewicz
Bozenna
B
Institute of Bioorganic Chemistry, Polish Academy of Sciences, ul. Noskowskiego 12/14,61-704 Poznan, Poland. bogolan@ibch.poznan.pl
Ostrowski
Tomasz
T
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005453:Fluorescence; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000737:chemistry*; D006564:Herpesviridae / Q000145:classification / Q000187:drug effects*; D006566:Herpesviridae Infections / Q000821:virology; D006801:Humans; D008826:Microbial Sensitivity Tests
D000998:Antiviral Agents; D015774:Ganciclovir; D000212:Acyclovir