Phenylpropenamide derivatives: Anti-hepatitis B virus activity of the Z isomer, SAR and the search for novel analogs

作者：Wang Peiyuan; Naduthambi Devan; Mosley Ralph T; Niu Congrong; Furman Phillip A; Otto Michael J; Sofia Michael J^*

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(15): 4642-4647.

DOI：10.1016/j.bmcl.2011.05.077

• Hepatitis B virus
• Antivirals
• Phenylpropenamides
• HBV inhibitors
• Pregenomic RNA packaging

Phenylpropenamides have been reported to be a class of non-nucleoside inhibitors of the hepatitis B virus (HBV). This class of compounds was explored with the objective of developing potent anti-HBV agents, with a novel mechanism of action, that could be combined with nucleos(t) ide analogs currently used to treat HBV infection. To accomplish this objective a series of substituted arylpropenamide derivatives were prepared and the E and Z geometrical isomers were separated. The structural identity of each of the E and Z isomers was determined by single crystal X-ray crystallography. Contrary to previous reports, the activity of this class of molecules resides in the Z isomer. Further structure-activity relationship studies around the active Z isomer identified compounds that displayed potent antiviral activity against HBV with EC(90) value of approximately 0.5 mu M in vitro. Attempts to develop ring constrained analogs did not lead to active HBV inhibitors.

• 出版日期2011-8-1