Design And Synthesis Of Dihydropyrimidine Anti - Hepatitis B Virus Compounds With Novel Aromatic Cycles

Despite the existence of an effective vaccination program, up to 400 million people worldwide are chronically infected with HBV currently. Moreover, the World Health Organisation estimates a death rate of 1 million people annually. At present, six drugs are licensed by the United States Food and Drug Administration(FDA).Because of high rates of resistance, poor tolerability and possible side effects, new therapeutic options are warranted.Heteroaryldihydropyrimidines(HAPs), inhibiting the proper formation of viral nucleocapsids which are the site of viral DNA replication, was discovered as highly potent non-nucleosidic inhibitors of HBV replication in vitro and in vivo. In this study, three categories analogs of HAPs targeting on the HBV capsids were designed by SAR and Pharmacophore and 33 compounds were synthesized. The structures of these compounds were identified by1H-NMR, MS.The antiviral activity of these compounds was tested in the transfected of HepG2.2.15 cells. 8 compounds exhibit the efficacity on blocking the HBV replication. The IC50 of 5 compounds were from 2μM to 7μM. The antiviral activity in vivo is under studying.