Pyrazolo[1′,5′:1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones as selective human A1 adenosine receptor ligands

A series of pyrazolo[1′,5′:1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones was synthesized and tested in radioligand binding assays to determine their affinities for the human adenosine A1, A2A, A2B and A3 receptors. Results indicated that this scaffold is appropriate for adenosine receptor subtype A1 ligands and that the best arranged groups around this scaffold are 3- and 4-pyridinyl at position 1, benzyl at position 3, hydrogen at position 6 and 3-thienyl or phenyl at position 9. The most interesting compounds showed Ki for A1 in the nanomolar range and an appreciable selectivity for other receptor subtypes.

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