Synthesis and antiviral activity of new phenylimidazopyridines and N -benzylidenequinolinamines derived by molecular simplification of phenylimidazo[4,5- g ]quinolines

Abstract Continuing our program of research concerning the antiviral activity of a wide series of new angular and linear azolo bicyclic and tricyclic derivatives, now we have simplified and modified the 4-chloro-2-(4-nitrophenyl)-3 H -imidazo[4,5- g ]quinoline 1 , which previously resulted the most active derivative, through either the elimination of the central ring or the opening of the imidazole ring, obtaining various imidazopyridines and N -benzylidenequinolinamines respectively. Title compounds were tested in cell-based assays for cytotoxicity and antiviral activity against representatives of two DNA virus families as wells as against representatives of RNA virus families containing single-stranded, either positive-sense (ssRNA + ) or negative-sense (ssRNA − ), and double-stranded genomes (dsRNA). Some imidazo[4,5- b ]pyridines emerged as new derivatives endowed with antiviral activity against Vaccinia Virus (VV) at concentrations ranging from 2 to 16 μM. In particular, compound 2b demonstrate to be about 10 times more potent than Cidofovir, used as reference drug. Similarly, the imidazo[4,5- c ]pyridines and N -benzylidenequinolinamines derivatives resulted active against Bovine Viral Diarrhoea virus (BVDV), at concentrations ranging from 1.2 to 28 μM. Above all compounds 1 , 3a and 3f showed an EC 50 of the same order of magnitude of the reference drug, the 2′-C-methyl-guanosine. Moreover, several N -benzylidenequinolinamines showed an interesting activity against Respiratory Syncytial Virus (RSV) at concentrations between 12 and 26 μM.