Alkylpurines as immunopotentiating agents. Synthesis and antiviral activity of certain alkylguanines.
Several simple 8-substituted 9-alkyl- and 7,8-disubstituted 9-alkylguanine derivatives were synthesized as potential antiviral agents. These were tested for antiviral protection against a lethal Semliki Forest virus (SFV) infection in mice, and their antiviral properties were evaluated from a structure-activity standpoint. In this model system, 9-alkylguanines with the alkyl chain consisting of four to six carbons were found to be the most active. Substitution of the 8-position of the purine ring did not enhance activity, with the exception of the 7-alkyl-8-oxo substituent. These data were found to support the hypothesis that guanines need not contain an intact carbohydrate moiety in order to exhibit antiviral activity by virtue of immune potentiation. Hence, phosphorylation of guanosine analogs that exhibit antiviral activity by a similar mechanism does not play a significant role.
Michael
M A
MA
ICN Nucleic Acid Research Institute, Costa Mesa, California 92626.
Cottam
H B
HB
Smee
D F
DF
Robins
R K
RK
Kini
G D
GD
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000494:pharmacology*; D000478:Alkylation; D018354:Alphavirus Infections / Q000188:drug therapy; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D007369:Interferon Inducers / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology*; D012672:Semliki forest virus; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D007369:Interferon Inducers; D011687:Purines; D006147:Guanine