Advanced generation of paeonol-phenylsufonyl derivatives as potential anti-HBV agents. Issue 49 (3rd May 2016) - Huang, Y. P.
Abstract : Among all the compounds we presented here, 8a showed the most potent inhibitory effect and highest selectivity index, which exceeds those of lamivudine (3TC) and our previously synthesized compound6f . Abstract : Hepatitis B virus (HBV) infection causes serious liver diseases, and the development of effective drugs for chronic hepatitis B treatment remains an important step towards the eradication of HBV worldwide. Recently, our group designed paeonol-phenylsulfonyl derivatives and found that the compound 2-acetyl-5-methoxyphenyl 4-methoxybenzenesulfonate (6f ) had the most potent antiviral effect against HBV, with an IC50 value of 0.36 μM and a high selectivity index (SI; TC50 /IC50 ) of 47.75. In this research, we modified compound6f with a 2-aminothiazole scaffold and generated 13 novel paeonol derivatives by utilizing various benzoyl and acyl chlorides. Among this new generation, compound 2-(2-benzamidothiazol-4-yl)-5-methoxyphenyl 4-methoxybenzenesulfonate (8a ) showed the highest SI value of 59.14 which exceeds those of compound6f and lamivudine (3TC), a commercially available antiviral drug. Hence, we believe that our studies may offer some useful information for the development of antiviral medicines.