piperidines and pyridazine

Two hundred forty pyridazinamine derivatives were tested for the ability to stabilize the antigenicity and infectivity of oral poliovirus vaccine subjected to 45 degrees C for 2 h. Seven compounds stabilized the antigenicity of all three vaccine strains and neutralized the viral particles in a way that is reversible by dilution. Of these, R 77975 (pirodavir) was selected for vaccine potency tests. Sabin type 2 and type 3 strains were subjected to 4, 25, 42, and 45 degrees C for 1 week in the presence and absence of R 77975. Although R 77975 particularly stabilized the infectivity of the most thermolabile vaccine strain (Sabin type 3), the protection did not exceed that of 1 M MgCl2. When virus was inactivated in the absence of R 77975, the native or N antigenicity changed in H antigenicity. However, in the presence of the capsid-binding compound, N antigenicity was preserved in particles that had lost infectivity.

Topics: Antiviral Agents; Drug Stability; HeLa Cells; Humans; Piperidines; Poliovirus; Poliovirus Vaccine, Oral; Pyridazines