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 indicati...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1978-12, Vol.21 (12), p.1218-1221
Main Authors: Baker, David C, Haskell, Theodore H, Putt, Sterling R
Format: Article
Language:English
Subjects:
Acylation
Adenosine Deaminase - metabolism
Antiviral Agents - chemical synthesis
Drug Stability
Solubility
Vidarabine - analogs & derivatives
Vidarabine - chemical synthesis
Vidarabine - metabolism
Vidarabine - pharmacology
Viral Plaque Assay
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00210a009