Adenosine receptors: synthesis, structure-activity relationships and biological activity of new 6-amino purine derivatives

The synthesis and evaluation of the biological activity of a series of pyridazin-3(2H)-one derivatives is reported. The compounds were tested in radioligand binding assays for affinity at A(1) and A(2A) adenosine receptors in bovine brain cortical membranes, and bovine brain striatal membranes, respectively. None of the compounds shows any affinity towards A(2A) receptor, while compounds in which the 6-chloro-pyridazin-3(2H)-one or 6-phenyl-pyridazin-3(2H)-one group is linked through a chain of two carbon atoms in the 6 position of the adenosine, show a good affinity towards A(1) adenosine receptor, particularly compound 8 in which a phenyl-pyridazinone group is present shows highest affinity with K-i values 6.6 nM. (C) Elsevier, Paris.