Coumarins hinged directly on benzimidazoles and their ribofuranosides to inhibit hepatitis C virus.

A new compound library that contained 20 hinged benzimidazole-coumarin hybrids and their β-d-ribofuranosides was established. The anti-hepatitis C virus (HCV) activity of all novel coumarin derivatives, which were obtained by use of organic synthetic methods, was tested. Two of these hybrids exhibited appealing EC50 values of as low as 3.

Structure-activity relationship of new anti-hepatitis C virus agents: heterobicycle-coumarin conjugates.

For establishment of the structure-activity relationship, 19 heterobicycle-coumarin conjugated compounds with the -SCH(2)- linker were synthesized and found to possess significant antiviral activities. Prominent examples included imidazopyridine-coumarin 12c, purine-coumarin 12d, and benzoxazole-coumarin 14c, which inhibited HCV replication at an EC(50) of 6.8, 2.

Synthesis of new benzimidazole-coumarin conjugates as anti-hepatitis C virus agents.

Nineteen new conjugated compounds were successfully synthesized by a one-flask method from benzimidazole and coumarin derivatives. A methylenethio linker was used to connect these two kinds of derivatives. In addition, substituted benzimidazol-2-thiones were also coupled with beta-D-glucose peracetate; the resultant glucosides were further converted to the corresponding 2-(methylthio)coumarin derivatives.