Carbocyclic Thymidine Analogues for Use as Potential Therapeutic Agents

Abstract

The discovery of azidothymidine's (AZT) activity against human immunodeficiency virus (HIV) provided strong rationale for the design of additional thymidine analogues. One drawback of many nucleoside analogues is the toxicity that often arises due to phosphorylation by cellular kinases. In order to overcome this problem, a number of truncated nucleosides lacking the 4′-hydroxymethyl group have been synthesized. In that regard, the synthesis and preliminary biological results for two truncated carbocyclic thymidine analogues are presented herein.

Keywords:

• Carbocyclic
• nucleosides
• pyrimidine
• SAHase
• neplanocin
• aristeromycin

Acknowledgments

This work was supported by the National Institutes of Health (RO1 CA97634, KSR). The authors also want to thank Dr. Sunny Zhou of Northeastern University for performing the SAHase assays.

In honor of and in celebration of Morris J. Robins’ 70th birthday.