Benzimidazole 2'-isonucleosides: Design, synthesis, and antiviral activity of 2-substituted-5,6-dichlorobenzimidazole 2'-isonucleosides

Article abstract of DOI:10.1080/15257770008033001

2,5,6-Trihalogenated benzimidazole-β-D-ribofuranosyl nucleosides and 2- substituted amino-5,6-dichlorobenzimidazole-β-L-ribofuranosyl nucleosides are potent and selective inhibitors of human cytomegalovirus (HCMV). The D- ribofuranosyl analogs are metabolized rapidly in vivo rendering them unsuitable as drug candidates. The primary source of instability is thought to be the anomeric bond. The synthesis of a series of chemically stable benzimidazole-2'-isonucleosides is presented. The synthetic schemes employed are based on nucleophilic displacements of a 2'-tosylate from carbohydrate intermediates with 2-bromo-5,6-dichlorobenzidazole. 2-Bromo and 2-isopropyl amino analogs with 3'- and 5'-oxo and deoxy substitutions were prepared. The benzimidazole-2'-isonucleosides presented here demonstrated reduced activity against HCMV when compared to other D-ribofuranosyl benzimidazole analogs. In addition, they were not found to be inhibitors of HIV.