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 erythro isomer being more potent than the threo one (8e, Ki = 0.11 microM vs 8t, Ki = 1.4 microM). However, the triazole derivatives did not show enhancement of inhibitory activity in comparison with the previously reported imidazole analogue 1b (Ki = 0.035 microM).
Adenosine deaminase inhibitors: synthesis, diastereoisomeric resolution and biological activity of 1-(2-hydroxy-3-nonyl)-1,2,4-triazole-3-carboxamide.
CAMAIONI, Emidio;
1997
Abstract
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 erythro isomer being more potent than the threo one (8e, Ki = 0.11 microM vs 8t, Ki = 1.4 microM). However, the triazole derivatives did not show enhancement of inhibitory activity in comparison with the previously reported imidazole analogue 1b (Ki = 0.035 microM).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
