Design, Synthesis, and Evaluation of Anti-HBV Activity of Hybrid Molecules of Entecavir and Adefovir: Exomethylene Acycloguanine Nucleosides and Their Monophosphate Derivatives

Abstract

Exomethylene acycloguanine nucleosides 4, 6 and its monophosphate derivatives 5, 7, and 8 have been synthesized. Mitsunobu-type coupling of 2-N-acetyl-6-O-diphenylcarbamoylguanine (11) with primary alcohols proceeded regioselectively to furnish the desired N(9)-substituted products in moderate yield. Evaluation of 4-8 for anti-HBV activity in HepG2 cells revealed that the phosphonate derivative 8 was found to exhibit moderated activity (EC50 value of 0.29 μM), but cytotoxicity (CC50 value of 39 μM) against the host cells was also observed.

Discovery of Oxime Ethers as Hepatitis B Virus (HBV) Inhibitors by Docking, Screening and In Vitro Investigation

“…Methods to stop and eliminate HBV DNA and cccDNA from HBV patients are still a great challenge for researchers. In searching for more effective anti-HBV agents, many significant anti-HBV non-nucleoside analogs from synthesized compounds [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ] and natural products [ 24 , 25 , 26 ] have been found. Some were designed according to their interactions with receptor by simulating screen [ 27 ].…”