New Pyrazolo[1′,5′:1,6]pyrimido[4,5-d]pyridazin-4 (3H)-ones Fluoroderivatives as Human A1 Adenosine Receptor Ligands

In this paper we report the synthesis and biological evaluation of a new series of pyrazolo[1',5': 1,6] pyrimido[4,5-d]pyridazin-4(3H)-ones as human A(1) adenosine receptor ligands. The tricyclic scaffold was modified at position 6 and 9 by introducing small alkyl chains and substituted phenyls. The most interesting compounds showed Ki for A(1) in the submicromolar range (0.105-0.244 mu M) and the most interesting term (compound 4c) combined an appreciable affinity for A(1) (Ki = 0.132 mu M) with a good selectivity toward A(2A) (43% inhibition at 10 mu M) and A(3) (46% inhibition at 10 mu M).