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

摘要

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 toward A_(2A)(43% inhibition at 10 μM) and A3 (46% inhibition at 10 μM).