Synthesis and pharmacological evaluation of novel 1- and 8-substituted-3-furfuryl xanthines as adenosine receptor antagonists.
The synthesis of an important set of 3-furfurylxanthine derivatives is described. Binding affinities were determined for rat A(1) and human A(2A), A(2B) and A(3) receptors. Several of the 3-furfuryl-7-methylxanthine derivatives showed moderate-to-high affinity at human A(2B) receptors, the most active compound (10d) having a K(i) of 7.4 nM for hA(2B) receptors, with selectivities over rA(1) and hA(2A) receptors up to 14-fold and 11-fold, respectively. Affinities for hA(3) receptors were very low for all members of the set.
Balo
María Carmen
MC
Departamento de Química Orgánica, Facultade de Farmacia, Universidade de Santiago de Compostela, E-15782 Santiago de Compostela, Spain.
Brea
José
J
Caamaño
Olga
O
Fernández
Franco
F
García-Mera
Xerardo
X
López
Carmen
C
Loza
María Isabel
MI
Nieto
María Isabel
MI
Rodríguez-Borges
José Enrique
JE
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D002460:Cell Line; D006801:Humans; D011485:Protein Binding; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; 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; 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