Antipicornavirus activity of some diaryl methanes and aralkylaminopyridines.
Sixteen diarylmethanes and ten aralkylaminopyridines were initially evaluated for their in vitro activity against rhinoviruses 1A, 2 and 64 and against coxsackievirus A21 and for their oral prophylactic and therapeutic activity in mice challenged with coxsackievirus A21. Based on these preliminary studies the diarylmethane (3,4-dichlorophenoxy)-(5 methylsulfonyl-2-pyridinyl)-methane and the aralkylaminopyridine (2-(3,4-dichlorobenzylamino)-5-methylsulfonylpyridine were compared with their oxygen bridged analogue 2-(3,4-dichlorophenoxy)-5-(methylsulfonyl)pyridine for in vitro activity against a larger number of picornaviruses and for their in vivo protective efficacy in dose response assays. All three compounds exhibit similar in vitro activity inhibiting 12 to 15 (52.2-65.3%) of the 23 picornaviruses tested at concentrations of less than 5.0 micrograms/ml. However, the aralkylaminopyridine was found to be the most active in vivo; significantly protecting coxsackievirus A21 challenged mice after a single oral dose of 37.5 mg/kg (P less than or equal to 0.05) and during a continuous oral dose regimen of as low as 18.8 mg/kg per day (P less than 0.01).
D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D004770:Enterovirus / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D010849:Picornaviridae / Q000187:drug effects*; D012229:Rhinovirus / Q000187:drug effects; D014709:Vero Cells
D000631:Aminopyridines; D000998:Antiviral Agents; D001559:Benzhydryl Compounds