Pyrimidinones. 1. 2-Amino-5-halo-6-aryl-4(3H)-pyrimidinones. Interferon-inducing antiviral agents.
Interferon induction and antiviral activity was discovered with 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone. An analogue study incorporating a series of 2-amino-5-substituted-6-arylpyrimidinones revealed that the most potent interferon inducers were mono- and difluorophenyl analogues. These same analogues were also potent antiviral agents against Semliki Forest virus and herpes simplex type 1. In addition the monomethoxyphenyl analogues were potent antiviral agents but weak interferon inducers. Relatively modest structural changes led to dramatic changes in bioactivity. There was a relatively poor correlation between levels of circulating interferons induced and systemic antiviral activity.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006219:Halogens / Q000138:chemical synthesis / Q000627:therapeutic use; D006561:Herpes Simplex / Q000188:drug therapy; D007369:Interferon Inducers / Q000627:therapeutic use*; D007370:Interferon Type I / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000627:therapeutic use*; D012672:Semliki forest virus; D013329:Structure-Activity Relationship; D014036:Togaviridae Infections / Q000188:drug therapy; D014777:Virus Diseases / Q000188:drug therapy*
D006219:Halogens; D007369:Interferon Inducers; D007370:Interferon Type I; D011744:Pyrimidinones; D007371:Interferon-gamma