The synthesis and preliminary in vitro evaluation of five metabolites of the A2A antagonist ST1535 (I) are reported. The metabolites, originating in vivo from enzymic oxidn. of the 2-Bu group of the parent compd., were synthesized from 6-chloro-2- iodo-9-methyl-9H-purine by selective C-C bond formation via halogen/magnesium exchange reaction and/or palladiumcatalyzed reactions. The metabolites, e.g., II, behaved in vitro as antagonist ligands of cloned human A2A receptor with affinities (Ki 7.5-53 nM) comparable to that of compd. I (Ki 10.7 nM), thus showing that the long duration of action of I could be in part due to its metabolites. General behavior after oral administration in mice was also analyzed.

Synthesis and Biological Evaluation of Metabolites of 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine (ST1535), A Potent Antagonist of the A2A Adenosine Receptor for the Treatment of Parkinson's Disease

Cabri W;
2013

Abstract

The synthesis and preliminary in vitro evaluation of five metabolites of the A2A antagonist ST1535 (I) are reported. The metabolites, originating in vivo from enzymic oxidn. of the 2-Bu group of the parent compd., were synthesized from 6-chloro-2- iodo-9-methyl-9H-purine by selective C-C bond formation via halogen/magnesium exchange reaction and/or palladiumcatalyzed reactions. The metabolites, e.g., II, behaved in vitro as antagonist ligands of cloned human A2A receptor with affinities (Ki 7.5-53 nM) comparable to that of compd. I (Ki 10.7 nM), thus showing that the long duration of action of I could be in part due to its metabolites. General behavior after oral administration in mice was also analyzed.
2013
Piersanti; Giovanni; Bartoccini; Francesca; Lucarini; Simone; Cabri W; Stasi; Maria Antonietta; Riccioni; Teresa; Borsini; Franco; Tarzia; Giorgio; Minetti; Patrizia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/756730
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