DISCOVERY OF IMIDAZOL[1,2-C]PYRIMIDIN-5(6H)-ONE HETEROSUBSTITUTED NUCLEOSIDE ANALOGS WITH POTENT ACTIVITY AGAINST HUMAN HEPATITIS-B VIRUS IN-VITRO

The in vitro antihepatitis B virus (HBV) activities of eleven novel im idazo[1,2-c]pyrimidin-5(6H)-one dideoxynucleoside analogues in which t he sugar ring is 1,3-dioxolane or 1,3-oxathiolane were compared in the chronically HBV-producing human cell line 2.2.15. Seven nucleoside an alogues 4, 9, 10, 15, 16, Is, and 24, of which 16 possesses the tra,ls relative stereochemistry, displayed good potency and selectivity towa rds HBV. The order of decreasing potency at the 90% extracellular DNA inhibition level was 15>16>24 approximate to 9>10>18. None of the test ed imidazo[1,2-c]pyrimidines inhibited the replication of HIV-1 in MT- 4 cells. (C) 1997, Elsevier Science Ltd.