Article,
New 2,6,9-trisubstituted adenines as adenosine receptor antagonists: a preliminary SAR profile
Purinergic Signal, 3 (4): 339-46 (September 2007)Lambertucci, Catia Cristalli, Gloria Dal Ben, Diego Kachare, Dhuldeo D Bolcato, Chiara Klotz, Karl-Norbert Spalluto, Giampiero Volpini, Rosaria Netherlands Purinergic signalling Purinergic Signal. 2007 Sep;3(4):339-46. Epub 2007 Sep 19..
Abstract
A new series of 2,6,9-trisubstituted adenines (5-14) have been prepared
and evaluated in radioligand binding studies for their affinity at
the human A(1), A(2A) and A(3) adenosine receptors and in adenylyl
cyclase experiments for their potency at the human A(2B) subtype.
From this preliminary study the conclusion can be drawn that introduction
of bulky chains at the N (6) position of 9-propyladenine significantly
increased binding affinity at the human A(1) and A(3) adenosine receptors,
while the presence of a chlorine atom at the 2 position resulted
in a not univocal effect, depending on the receptor subtype and/or
on the substituent present in the N (6) position. However, in all
cases, the presence in the 2 position of a chlorine atom favoured
the interaction with the A(2A) subtype. These results demonstrated
that, although the synthesized compounds were found to be quite inactive
at the human A(2B) subtype, adenine is a useful template for further
development of simplified adenosine receptor antagonists with distinct
receptor selectivity profiles.
