ABSTRACT
The synthesis of original imidazo[1,2-a]pyridines bearing a thioether side chain at the 3 position and their antiviral activity are reported. From the synthesized compounds, 4, 15, and 21 were highly active against human cytomegalovirus with a therapeutic index superior to 150. These compounds also showed pronounced activity against varicella-zoster virus. Their structure-activity relationship is discussed.
Subject(s)
Antiviral Agents/chemical synthesis , Imidazoles/chemical synthesis , Pyridines/chemical synthesis , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Cell Line , Chlorocebus aethiops , Cytomegalovirus/drug effects , Drug Evaluation, Preclinical , HeLa Cells , Herpesvirus 3, Human/drug effects , Humans , Imidazoles/chemistry , Imidazoles/pharmacology , Inhibitory Concentration 50 , Pyridines/chemistry , Pyridines/pharmacology , Structure-Activity Relationship , Vero CellsABSTRACT
The synthesis and the antiviral activities of C-3 acyclic nucleoside analogues of imidazo[1,2-a]pyridine and pyrimidine are reported. From these compounds, 20, 21, 22, 23, 28, and 34 showed a specific activity against cytomegalovirus and/or varicella-zoster virus.
Subject(s)
Antiviral Agents/chemical synthesis , Nucleosides/chemical synthesis , Pyridines/chemistry , Pyridines/chemical synthesis , Pyrimidines/chemical synthesis , Animals , Antiviral Agents/pharmacology , Chlorocebus aethiops , HeLa Cells , Humans , Nucleosides/pharmacology , Pyridines/pharmacology , Pyrimidines/pharmacology , Structure-Activity Relationship , Tumor Cells, Cultured , Vero CellsABSTRACT
Three potentially antiviral imidazo[1,2-a]pyridine derivatives of increasing hydrophilicity were tested in their interactions with model membranes and synthetic oligonucleotides. It was shown that the most hydrophobic derivative [1], located in the depth of the bilayer only induces minor membrane damages. The molecule [2], only poorly hydrophobic, integrates also the bilayer in the medium part of the chains while the most hydrophilic [3] exhibits fluidizing and slightly detergent properties. In the presence of synthetic oligonucleotide ACATGT no intercallation of the three derivatives was evidenced. By considering their antiviral activity in the absence of evident mitogenic properties, another mechanism of action was proposed.
