Adenosine Deaminase Inhibitors: Synthesis and Biological Evaluation of Unsaturated, Aromatic, and Oxo Derivatives of (+)-erythro-9-(2‘S-Hydroxy-3‘R-nonyl)adenine [(+)-EHNA]
- 1 November 2000
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 43 (24) , 4694-4700
- https://doi.org/10.1021/jm0002533
Abstract
The synthesis and biological evaluation of three classes of chain-modified derivatives of (+)-EHNA are described. Among the 5‘,6‘-unsaturated derivatives, the Z-isomer was the most potent inhibitor of adenosine deaminase (ADA) but 3-fold less active than (+)-EHNA. Several 9-aralkyladenines (ARADs) have been prepared, and their inhibitory activity was determined. A minimum of two carbon atoms separating the aromatic ring from the adenine-bearing carbon (C-3‘) was found to be essential for ADA activity equal to or slightly greater than that of (+)-EHNA. Finally, replacement of the C-5‘ carbon with an oxygen resulted in reduced potency.Keywords
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