[[(4,5-Dihydro-2-oxazolyl)phenoxy]alkyl]isoxazoles. Inhibitors of picornavirus uncoating.
A series of [[(4,5-dihydro-2-oxazolyl)phenoxy]alkyl]isoxazoles has been synthesized and evaluated as antipicornavirus agents. The effect of alkyl groups in the 4- and 5-position of the oxazoline ring, as well as the alkyl chain length, on antiviral activity was examined. Compound 14 was evaluated in vivo and was found to significantly reduce mortality at an oral dose of 4 mg/kg in mice infected intracerebrally with poliovirus-2. Compound 14 was also effective in preventing paralysis when administered intraperitoneally to mice infected subcutaneously with a lethal dose of ECHO-9 virus. On the basis of the results of these studies, compound 14 is a strong candidate for clinical evaluation as a systemic agent for the treatment of picornavirus infections.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D010080:Oxazoles / Q000627:therapeutic use*; D010850:Picornaviridae Infections / Q000188:drug therapy*; D017955:Poliovirus / Q000187:drug effects / Q000502:physiology; D012229:Rhinovirus / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D007555:Isoxazoles; D010080:Oxazoles; C045978:disoxaril