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• W2325644863 abstract "Heat-stress cognate 70 (Hsc70) is a host protein required for hepatitis B virus (HBV) replication, and oxymatrine (1) suppresses Hsc70 expression. Taking Hsc70 as a target against HBV, 22 analogues of 1 defined with substituents at position 1, 13, or 14 were synthesized and evaluated for their activity on Hsc70 mRNA expression. The SAR revealed that (i) the oxygen atom at the 1-position was not essential, (ii) increasing electron density on the ring D reduced the activity, and (iii) introducing a proper substituent at the 13- and/or 14-position(s), especially electron-withdrawing groups, might enhance the activity. Among the analogues, 6b possessing 13-ethoxyl afforded an increased activity in respect to 1. Importantly, it was active for either wild-type or lamivudine-resistant HBV, as its target is host Hsc70 but not viral enzymes. LD(50) of 6b in mice was over 750 mg/kg in oral route. We consider compound 6b promising for further investigation." @default.
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• W2325644863 date "2011-01-10" @default.
• W2325644863 modified "2023-10-18" @default.
• W2325644863 title "Design and Synthesis of Oxymatrine Analogues Overcoming Drug Resistance in Hepatitis B Virus through Targeting Host Heat Stress Cognate 70" @default.
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• W2325644863 doi "https://doi.org/10.1021/jm101325h" @default.
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