Synthesis of new 2-phenyladenines and 2-phenylpteridines and biological evaluation as adenosine receptor ligands.
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, N(6)-cycloalkyl- or N(6)-alkyl-2-phenyladenines showed a very high affinity and selectivity for A(1) adenosine receptors. We demonstrate also that the 9-benzyl substituent is crucial for conferring high affinity for A(3) receptors to molecules having a 2-phenyladenine-like nucleus.
Giorgi
Irene
I
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Pisa, Italy. igiorgi@farm.unipi.it
Biagi
Giuliana
G
Livi
Oreste
O
Leonardi
Michele
M
Scartoni
Valerio
V
Pietra
Daniele
D
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D003412:Cricetulus; D008024:Ligands; D011621:Pteridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D013329:Structure-Activity Relationship
D008024:Ligands; D011621:Pteridines; D018047:Receptors, Purinergic P1; D000225:Adenine