3,4-Dihydro-2-phenyl-2H-pyrano[2,3-b]pyridines with potent antirhinovirus activity.
A general synthesis to the title compounds 1, substituted in the 6-position and on the phenyl ring, is outlined. Eighteen analogues were compared with respect to in vitro activity against rhinovirus types 1A, 9, and 64. Compounds 1c and 1h, the 6-bromo- and 6-(methylsulfonyl)-3',4'-dichlorophenyl analogues, afforded median MIC50 values against 23 rhinovirus serotypes of 0.05 and 0.13 micrograms/mL, respectively. Mice dosed orally with 200 mg/kg of 1c or 1h exhibited serum levels well in excess of each compound's MIC50, indicating that some analogues have the potential to be orally effective drugs.
D000818:Animals; D000998:Antiviral Agents / Q000097:blood / Q000138:chemical synthesis / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D051379:Mice; D011725:Pyridines / Q000097:blood / Q000138:chemical synthesis / Q000494:pharmacology*; D012229:Rhinovirus / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D011725:Pyridines