Prodrugs of 9-beta-D-arabinofuranosyladenine. 1. Synthesis and evaluation of some 5'-(O-acyl) derivatives.
A number of 5'-(O-acyl) derivatives of 9-beta-D-arabinofuranosyladenine (ara-A, VIRA-A) (2a-k) were prepared by direct acylation of the parent nucleoside 1 in pyridine-N,N-dimethyliformamide. These compounds, designed as prodrugs for 1, offer a range of solubilities and lipophilicities indicating for several examples improved solubility and the potential for improved membrane transport over 1. All are resistant to deactivation by adenosine deaminase. Of special interest is the 5'-(O-valeryl) derivative 2d that shows a marked increase in antiviral activity over 1.
D000215:Acylation; D000243:Adenosine Deaminase / Q000378:metabolism; D000998:Antiviral Agents / Q000138:chemical synthesis; D004355:Drug Stability; D012995:Solubility; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D000243:Adenosine Deaminase; D014740:Vidarabine