Pyrazolo-triazolo-pyrimidines as adenosine receptor antagonists:
Effect of the N-5 bond type on the affinity and selectivity at the
four adenosine receptor subtypes
Purinergic Signal, 4 (1):
39-46 (March 2008)Bolcato, Chiara Cusan, Claudia Pastorin, Giorgia Spalluto, Giampiero
Cacciari, Barbara Klotz, Karl Norbert Morizzo, Erika Moro, Stefano
Netherlands Purinergic signalling Purinergic Signal. 2008 Mar;4(1):39-46.
Epub 2007 Jul 25..Abstract
In the last few years, many efforts have been made to search for potent
and selective human A(3) adenosine antagonists. In particular, one
of the most promising human A(3) adenosine receptor antagonists is
represented by the pyrazolo-triazolo-pyrimidine family. This class
of compounds has been strongly investigated from the point of view
of structure-activity relationships. In particular, it has been observed
that fundamental requisites for having both potency and selectivity
at the human A(3) adenosine receptors are the presence of a small
substituent at the N(8) position and an unsubstitued phenyl carbamoyl
moiety at the N(5) position. In this study, we report the role of
the N(5)-bond type on the affinity and selectivity at the four adenosine
receptor subtypes. The observed structure-activity relationships
of this class of antagonists are also exhaustively rationalized using
the recently published ligand-based homology modeling approach.