Synthesis and pharmacological evaluation of novel 1,3,8- and 1,3,7,8-substituted xanthines as adenosine receptor antagonists.
A number of novel xanthines bearing a variety of substituents at positions 1, 3, 7 and 8 were prepared and evaluated for their binding affinity to the human adenosine receptor A(1), A(2A), A(2B) and A(3) subtypes. Several of the 1,3,8- and 1,3,7,8-substituted xanthines showed moderate-to-high affinity at human A(2B) and A(1) receptors, with the most active compound (14q) having a pK(i) of 7.57 nM for hA(2B) receptors and a selectivity over hA(2A) receptors of 8.1-fold and hA(1) receptors of 3.7-fold.
CIQ-Departamento de Química, Facultade de Ciencias, Universidade de Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal.
José Enrique
JE
Rodríguez-Borges
Xerardo
X
García-Mera
María Carmen
MC
Balo
José
J
Brea
Olga
O
Caamaño
Franco
F
Fernández
Carmen
C
López
María Isabel
MI
Loza
María Isabel
MI
Nieto
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D000893:Anti-Inflammatory Agents; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D014970:Xanthines