Adenosine deaminase inhibitors: Synthesis and biological evaluation of unsaturated, aromatic, and oxo derivatives of (+)-erythro-9-(2 ' S-hydroxy-3 'R-nonyl)adenine [(+)-EHNA]

The synthesis and biological evaluation of three classes of chain-modified derivatives of(+)EHNA are described. Among the 5',6'-unsaturated derivative s, the Z-isomer was the most potent inhibitor of adenosine deaminase (ADA) but 3-fold less active than (+)-EHNA. Several 9-aralkyladenines (ARADs) hav e been prepared, and their inhibitory activity was determined. A minimum of two carbon atoms separating the aromatic ring from the adenine-bearing car bon (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.