Synthesis Of Some Novel Benzimidazole Derivatives And Theire Biological Performance Against Coxsackie Virus B3

Coxsackie virus B3 (CVB3), a non-enveloped single positive-strand RNA belonging to picornaviridea family, is always associated with the cause of virus-induced epidemic pleurodynia, myocarditis and endocarditis, respiratory disorders, and kidney, pancreas, and liver disorders. Few drugs are effective to the CVB3-infected human by now.According to our previous research, 2-aryl-1H-benzimidazole-4-carboxamide derivatives have a strong antiviral activity against Coxsackie virus B3 (CVB3). In addition, we found that 2-fluorophenyl group plays an important role in the antiviral biological properties. Furan can restrain acyl coenzyme and disturb bacteria metabolize. Therefore, a furyl group was introduced as the biochemical functional group into the designed molecule in order to develop novel compounds against Coxsackie virus B3. In the same way, we introduced (L)-2-amino-1-paranitrophenyl-1, 3-propnebiol, (E)-2-amino-1-prachloro- phenyl-1-propanol, 6APA, and 7ACA, which are common medical intermediates. The target products were expected to have greater medical activity.The paper reported the synthesis of over 20 kinds of novel benzimidazole derivatives. The data of IR, 1H-NMR, MS and Elemental Analysis testify structures of these novel compounds. Many of these new compounds were evaluated acting as antivirus against Coxsackie virus B3 (CVB3) in VERO cells. It was found that most of them (except compound 26) have inhibitory activity against CVB3. Compounds 15, 25 and 27 have excellent IC50 values (1.76, 1.06 and 1.76μg/ml, respectively), more active than RBV with IC50 value of 353.55μg/ml.SAR (Structure and Activity Relationship) was studied. The results confirmed the conclusion that we obtained in our previous work, and indicated that 2-aryl-1H- benzimidazole-4-carboxamide derivatives are much better than 3- and 4-pyridyl derivatives, and the introduction of 2-fluorophenyl, (L)-2-amino-1- paranitrophenyl-1, 3-propnebiol and (E)-2-amino-1-prachlorophenyl-1-propanol improves biological activity and selectivity greatly.These evident prove that the groups and structures of benzimidazole derivatives are related to the biological activity for inhibiting CVB3. And all of the data show the potential values of pharmaceutic applications in the coming future.