The Synthesis and Biological Evaluation of Benzamide Riboside and Its Phosphordiamidates Prodrugs

Abstract

In order to overcome the drug resistance and enhance the membrane penetration ability of benzamide riboside [BR, (1-β-D-ribofuranosyl) benzene-3-carboxamide], which is a novel C-glycoside analogue of nicotinamide riboside and has excellent cytotoxic activity, we designed and synthesized two phosphordiamidates (1a and 1b) as prodrugs to deliver phosphorylated BR into cells. However, the bioactivity evaluation shows that 1a and 1b have lower biological activity (IC₅₀ > 200 μM and 173 μM, respectively) compared to BR. This might be due to the fact that 1a and 1b could only serve as the BR depot form and thus could not be metabolized to the phosporylatd benzamide riboside.

Keywords:

• Benzamide riboside prodrug
• benzylphosphordiamidate

Acknowledgments

The authors gratefully acknowledge the National Natural Science Foundation of China (NSFC20132020, 20572060) and National Department of Science and Technology (2005CCA03400) for financial support of this work.