Synthesis and biological assays of a series of 2-phenylpteridine derivatives are described to compare their affinities to adenosine receptors with those of the corresponding adenines, purposely prepared, and 8-azaadenines previously described. This study demonstrates that the enlargement of the five-membered ring of the adenine nucleus to a six-membered one is a modification that does not allow the molecules to maintain high activity towards adenosine receptors; in fact, pteridine derivatives did not show themselves to be good adenosine receptor ligands. On the contrary, N6-cycloalkyl- or N6-alkyl-2-phenyladenines showed a very high affinity and selectivity for A1 adenosine receptors. We demonstrate also that the 9-benzyl substituent is crucial for conferring high affinity for A3 receptors to molecules having a 2-phenyladenine-like nucleus.
Synthesis of new 2-phenyladenines and 2-phenylpteridines and biological evaluation as adenosine receptor ligands
GIORGI, IRENE;PIETRA, DANIELE
2007-01-01
Abstract
Synthesis and biological assays of a series of 2-phenylpteridine derivatives are described to compare their affinities to adenosine receptors with those of the corresponding adenines, purposely prepared, and 8-azaadenines previously described. This study demonstrates that the enlargement of the five-membered ring of the adenine nucleus to a six-membered one is a modification that does not allow the molecules to maintain high activity towards adenosine receptors; in fact, pteridine derivatives did not show themselves to be good adenosine receptor ligands. On the contrary, N6-cycloalkyl- or N6-alkyl-2-phenyladenines showed a very high affinity and selectivity for A1 adenosine receptors. We demonstrate also that the 9-benzyl substituent is crucial for conferring high affinity for A3 receptors to molecules having a 2-phenyladenine-like nucleus.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
