Interferon induction by 5-halo-6-phenyl pyrimidinones.
The interferon inducing characteristics of a new series of 6-phenyl pyrimidinol compounds are described and compared against a previously identified pyrimidine, 2-amino-5-bromo-6-methyl-4-pyrimidinol (ABMP). Interestingly, a split in ability to induce interferon but not in vivo antiviral activity was observed in the newest compounds. One representative compound, 2-amino-5-bromo-6-phenyl-4-pyrimidinol (ABPP) induced high levels of serum interferon in mice, cats and cattle in vivo and human lymphoid tissue in vitro and was consistently more active than ABMP. Another representative compound, 2-amino-5-iodo-6-phenyl-4-pyrimidinol (AIPP) was a poor interferon inducer in every system evaluated yet was as active as an in vivo antiviral agent as ABPP or ABMP. The serum interferon response induced by both ABMP and ABPP appeared to originate from an antilymphocyte serum resistant but radiosensitive cell population in the thymus and spleen. These results suggest that the antiviral activity of this group of agents is mediated by both interferon and interferon independent mechanisms.
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002415:Cats; D002417:Cattle; D002478:Cells, Cultured; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004686:Encephalomyocarditis virus / Q000254:growth & development; D005260:Female; D005347:Fibroblasts; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology; D007369:Interferon Inducers; D007739:L Cells; D051379:Mice; D008813:Mice, Inbred ICR; D011743:Pyrimidines / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology*; D012672:Semliki forest virus / Q000254:growth & development; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development
D000998:Antiviral Agents; D006846:Hydrocarbons, Halogenated; D007369:Interferon Inducers; D011743:Pyrimidines; D011744:Pyrimidinones; C014927:2-amino-5-bromo-6-methyl-4-pyrimidinol; C033561:2-amino-5-iodo-6-phenyl-4-pyrimidinone; D003596:Cytosine; C033560:bropirimine