Synthesis of novel 1-alkyl-8-substituted-3-(3-methoxypropyl) xanthines as putative A(2B) receptor antagonists.
In order to identify a high-affinity, selective antagonist for the A(2B) subtype adenosine receptor, more than 40 1,8-disubstituted-3-(3-methoxypropyl) xanthines were prepared and evaluated for their binding affinity at recombinant human adenosine receptors, mainly of the A(2A) and A(2B) subtypes. Some of the 1-ethyl-3-(3-methoxypropyl)-8-aryl substituted derivatives 15(a-m) showed moderate-to-high affinity at human A(2B) receptors, with compound 15d showing A(2B) selectivity over the other A receptors assayed (A(1), A(2A), A(3)) of 34-fold or over.
Nieto
María Isabel
MI
Departamento de Química Fundamental, Facultade de Química, Universidade de A Coruña, Coruña, Spain.
Balo
María Carmen
MC
Brea
José
J
Caamaño
Olga
O
Cadavid
María Isabel
MI
Fernández
Franco
F
Mera
Xerardo García
XG
López
Carmen
C
Rodríguez-Borges
José Enrique
JE
D058917:Adenosine A2 Receptor Antagonists; D006367:HeLa Cells; D006801:Humans; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D058917:Adenosine A2 Receptor Antagonists; D011720:Pyrazoles; D014970:Xanthines