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

• Published in: Purinergic signalling 2008-03, Vol.4 (1), p.39-46
• Main Authors: Bolcato, Chiara, Cusan, Claudia, Pastorin, Giorgia, Spalluto, Giampiero, Cacciari, Barbara, Klotz, Karl Norbert, Morizzo, Erika, Moro, Stefano
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer Research; Human Physiology; Neurosciences; Original Paper; Pharmacology/Toxicology
• ISSN: 1573-9538; 1573-9546
• DOI: 10.1007/s11302-007-9058-y

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.