5-Iodo-2-arylalkylthio-6-aryl pyrimidin-4(3H)-ones as non-nucleoside anti-HBV agents

A series of 5-iodo-2-arylalkylthio-6-aryl pyrimidin-4(3H)-ones, which can be considered as S-DABO derivatives, have been synthesized and their antiviral effect on extracellular HBV DNA was evaluated using the HepAD38 cell system. Compounds 6d1 and 6e3 exhibited more potent anti-HBV activity than lamivudine with EC50 values of 0.376 mu M and 0.469 mu M, respectively. In addition, inhibition of intracellular HBV DNA, pgRNA, HBeAg and HBsAg of compounds 6d1 and 6e3 was examined to initially infer the action mechanism. RT-PCR analysis of pgRNA demonstrated that these new S-DABO analogues could not interfere with HBV transcription. TRFIA analysis revealed that compounds 6d1 and 6e3 effectively reduced the secretion of HBeAg. These results demonstrated that 5-iodo-2-arylalkylthio-6-aryl pyrimidin-4(3H)-ones possess anti-HBV abilities and could be used as potential agents against HBV infection with an additional merit of low cytotoxicity.