Two types of adenosine receptor ligands were designed, i.e., 9H-purine and 1H-imidazo[4,5-c]pyridines, to obtain selective A2A antagonists, and we report here their synthesis and binding affinities for the four adenosine receptor subtypes A1, A2A, A2B and A3. The design was carried out on the basis of the molecular modeling of a number of potent adenosine receptor antagonists described in the literature. Three compounds (25b-d) showed an interesting affinity and selectivity for the A2A subtype. One of them, i.e., ST1535 (2-n-butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine, 25b) (Ki A2A ) 6.6 nM, Ki A1/A2A ) 12; Ki A2B/A2A ) 58; Ki A3/A2A > 160), was selected for in vivo study and shown to induce a dose-related increase in locomotor activity, suggestive of an A2A antagonist type of activity.

2-n-Butyl- 9-methyl-8-(1,2,3)triazol-2-yl-9H-purin-6-ylamine and Analogues as A2A Adenosine Receptor Antagonists. Design, Synthesis, and Pharmacological Characterization

GIORGI, LUCA;PIERSANTI, GIOVANNI;BARTOCCINI, FRANCESCA;TARZIA, GIORGIO
2005

Abstract

Two types of adenosine receptor ligands were designed, i.e., 9H-purine and 1H-imidazo[4,5-c]pyridines, to obtain selective A2A antagonists, and we report here their synthesis and binding affinities for the four adenosine receptor subtypes A1, A2A, A2B and A3. The design was carried out on the basis of the molecular modeling of a number of potent adenosine receptor antagonists described in the literature. Three compounds (25b-d) showed an interesting affinity and selectivity for the A2A subtype. One of them, i.e., ST1535 (2-n-butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine, 25b) (Ki A2A ) 6.6 nM, Ki A1/A2A ) 12; Ki A2B/A2A ) 58; Ki A3/A2A > 160), was selected for in vivo study and shown to induce a dose-related increase in locomotor activity, suggestive of an A2A antagonist type of activity.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11576/1886722
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