Adenosine deaminase inhibitors: Synthesis, diastereoisomeric resolution and biological activity of 1-(2-hydroxy-3-nonyl)-1,2,4-triazole-3-carboxamide

The synthesis and the diastereoisomeric resolution of 9-(2-hydroxy-3-nonyl)-1,2,4-triazole-3-carboxamide (8e and 8t) were undertaken in order to investigate the structural requirements of the adenosine deaminase inhibitory site, through simplification of the purine moiety of 9-(2-hydroxy-3-nonyl)adenine (1a, EHNA). The new compounds resulted to be good inhibitors of the enzyme, the erytho isomer being more potent than the threo one (8e, Ki=0.11 mu M vs 8t, Ki=1.4 mu M). However, the triazole derivatives did not show enhancement of inhibitory activity in comparison with the previously reported imidazole analogue 1b (Ki=0.035 mu M).