Recent developments in the field of A2A and A3 adenosine receptor antagonists.
In the last years adenosine receptors have been extensively studied, and mainly at present we understand the importance of A(2A) and A(3) adenosine receptors. A(2A) selective adenosine receptors antagonists are promising new drugs for the treatment of Parkinson's disease, while A(3) selective adenosine receptors antagonists have been postulated as novel anti-inflammatory and antiallergic agents; recent studies also indicated a possible employment of these derivatives as antitumour agents. Lately different classes of compounds have been identified as potent A(2A) and A(3) antagonists. In this article we report the past and present efforts which led to development of more potent and selective A(2A) and A(3) antagonists. Our group has mainly worked on the pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine nucleus both as A(2A) and A(3) antagonists, aiming to improve the affinity, selectivity and the hydrophilic profile. In fact, we have synthesised several compounds endowed with high affinity and selectivity versus A(2A) adenosine receptors, as 2, 2a-c (K(i)A(2A)=0.12-0.19 nM), or A(3) adenosine receptors, as 4p (K(i)A(3)=0.01 nM) and 4q (K(i)A(3)=0.04 nM).
Baraldi
Pier Giovanni
PG
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via fossato di Mortara 17-19, 44100, Ferrara, Italy. pgb@dns.unife.it
Tabrizi
Mojgan Aghazadeh
MA
Bovero
Andrea
A
Avitabile
Barbara
B
Preti
Delia
D
Fruttarolo
Francesca
F
Romagnoli
Romeo
R
Varani
Katia
K
Borea
Pier Andrea
PA
D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000378:metabolism; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D006571:Heterocyclic Compounds; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D043684:Receptor, Adenosine A3; D014970:Xanthines