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

• Published in: European journal of medicinal chemistry 2014-09, Vol.84, p.8-16
• Main Authors: Loddo, Roberta, Briguglio, Irene, Corona, Paola, Piras, Sandra, Loriga, Mario, Paglietti, Giuseppe, Carta, Antonio, Sanna, Giuseppina, Giliberti, Gabriele, Ibba, Cristina, Farci, Pamela, La Colla, Paolo
• Format: Article
• Language: English
• Subjects: Aminoquinolines - chemical synthesis; Aminoquinolines - chemistry; Aminoquinolines - pharmacology; Animals; Antiviral activity; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Bovine viral diarrhoea virus (BVDV); Cattle; Cell Line; Cell Survival - drug effects; Coxsackie virus type B5 (CVB-5); DNA Viruses - drug effects; Dogs; Dose-Response Relationship, Drug; Herpes simplex virus type 1 (HSV-1); Humans; Imidazoles - chemical synthesis; Imidazoles - chemistry; Imidazoles - pharmacology; Microbial Sensitivity Tests; Molecular Structure; N-benzylidenequinolinamines; Phenylimidazopiridines; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; Respiratory syncytial virus (RSV); RNA Viruses - drug effects; Structure-Activity Relationship; Vaccinia virus (VV)
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.07.011

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)-3H-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 EC50 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. [Display omitted] •In this study we prepared novel imidazopyridines and N-benzylidenequinolinamines.•All the derivatives have been investigated for different antiviral activities.•One compound showed an activity 10 times more potent than Cidofovir against VV.•Some compounds showed the same order of magnitude of the reference drug, the 2′-C-methyl-guanosine against BVDV.