Abstract
New conjugated compounds containing the coumarin moiety attached to mono- or bis-heterocyles have been synthesized. In >100 new conjugates of five categories, some of them exhibit significant and appealing activity against Hepatitis C Virus (HCV). The heterocycles therein include adenine, benzimidazole, benzothiazole, benzoxazole, guanine, hypoxanthine, imidazole, imidazopyridine, and purine. Use of the thiomethylene (–SCH2 –) linker to connect a coumarin moiety and a purine or imidazole nucleus leads to the conjugates with greater activity and selectivity than others. Various substituents, including CH3 , F, Cl, Br, OCH3 , OAc, CO2H, COPh, NO2, β-D-glucose, and β-D-ribofuranose, are also attached to the core nuclei. Incorporation of a halogen substituent (particularly the Br) onto the coumarin nucleus generally enhances the anti-HCV activity from double-digit to single-digit of µM potency. The structure-activity relationship is established, which is of value to the development of new anti-HCV drugs.