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.
Piersanti, Giovanni, Bartoccini, Francesca, Lucarini, Simone, et al. (2013). 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. JOURNAL OF MEDICINAL CHEMISTRY, 56(13), 5456-5463 [10.1021/jm400491x].
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
