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 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).
Volpini
R
R
Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
Camaioni
E
E
Lupidi
G
G
Vittori
S
S
Cristalli
G
G
D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
C110284:1-(2-hydroxy-3-nonyl)-1,2,4-triazole-3-carboxamide; D058892:Adenosine Deaminase Inhibitors; D004791:Enzyme Inhibitors; D005233:Fatty Alcohols; D014230:Triazoles