Chemical Research in Chinese Universities ›› 2014, Vol. 30 ›› Issue (5): 749-754.doi: 10.1007/s40242-014-4183-y

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Synthesis and Biological Evaluation of Entecavir 4'-Ester Derivatives

FENG Deri, LIU Jiaan, LIANG Shuang, WANG Yanyan, XU Youjun   

  1. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China
  • Received:2014-05-14 Revised:2014-07-30 Online:2014-10-01 Published:2014-09-22
  • Contact: XU Youjun E-mail:xuyoujun65@163.com
  • Supported by:

    Supported by the National Natural Science Foundation of China(No.51209024) and the Science and Technology Plan of Sichuan Province, China(No.2010JY0122).

Abstract:

Entecavir can significantly inhibit the replication of HBV-DNA, reduce the HBV-DNA level in blood serum. But suffering from low oral bioavailability, entecavir has low intestinal membrane permeability and poor metabolic stability. In this study, 12 different derivatives of entecavir 4'-ester were regioselectively synthesized and their apical-to-basolateral permeabilities across Caco-2 cells and HBV-DNA inhibitory efficacies were evaluated. Most of the compounds showed high permeabilities across Caco-2 cells compared with entecavir, compounds 5b and 5e also exhibited comparable anti-HBV activities with that of entecavir, especially.

Key words: Entecavir, Anti-HBV activity, Intestinal membrane permeability