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 A1 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 A1 in the submicromolar range (0.105–0.244 μM) and the most interesting term (compound 4c) combined an appreciable affinity for A1 (Ki = 0.132 μM) with a good selectivity towardA2A (43% inhibition at 10 μM) and A3 (46% inhibition at 10 μM).