Design, synthesis, testing, and quantitative structure-activity relationship analysis of substituted salicylaldehyde Schiff bases of 1-amino-3-hydroxyguanidine tosylate as new antiviral agents against coronavirus.

Further modifications of the structural features of Schiff bases of hydroxyaminoguanidines (SB-HAG) led to nine substituted salicylaldehyde Schiff bases of HAG (SSB-HAG) derivatives and three other SB-HAG derivatives. These new compounds were tested for the first time against infection by a coronavirus, mouse hepatitis virus (MHV). The most active compound, 2 [1-[(3'-allyl-2'-hydroxybenzylidene)amino]- 3-hydroxyguanidine], against the growth of MHV is about 376 times more active than hydroxyguanidine and about 564 times more active than HAG itself when the TCID50 values are compared. Plaque assays of MHV released from cells treated with these compounds suggest that SSB-HAG tosylate may inhibit the transcription of viral RNAs in virus-infected cells. Quantitative structure-activity relationship (QSAR) analyses of two subsets show that the inhibitory activities correlate well with the electronic and the lipophilic parameters. The structural requirements for the antiviral activity of substituted SSB-HAG tosylate against coronaviral infection are stringent according to the inhibitory activities and QSAR analysis of these new compounds.