8-Substituted-9-deazaxanthines as adenosine receptor ligands: design, synthesis and structure-affinity relationships at A2B.
A number of 8-substituted-9-deazaxanthine derivatives (1,3-dialkyl-6-substituted-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-diones) were prepared and tested for their antagonistic activity at the recombinant human adenosine receptors, in particular at the A(2B) and A(2A) receptor subtypes. Compounds endowed with micromolar to nanomolar binding affinities, but with poor A(2B)/A(2A) selectivity, were obtained. Preliminary quantitative structure-affinity relationships suggested that the binding potency at the A(2B) receptor is mainly modulated by the electronic and lipophilic properties of the ligands.
Dipartimento Farmacochimico, Università di Bari, via Orabona 4, 70125 Bari, Italy. carotti@farmchim.uniba.it
Angelo
A
Carotti
Angela
A
Stefanachi
Enrique
E
Raviña
Eddy
E
Sotelo
Maria Isabel
MI
Loza
Maria Isabel
MI
Cadavid
Nuria B
NB
Centeno
Orazio
O
Nicolotti
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D008024:Ligands; D011485:Protein Binding / Q000502:physiology; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis* / Q000378:metabolism*
D058917:Adenosine A2 Receptor Antagonists; D008024:Ligands; D043704:Receptor, Adenosine A2B; D014970:Xanthines