Further studies on pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones as potent and selective human A1 adenosine receptor antagonists.

A new series of pyrazolo[1',5':1,6]pyrimido[4,5-dlpyridazin-4(3H)-ones was synthesized and tested in radioligand binding assays on human A(1), A(2A) and A(3) adenosine receptors. Most of the compounds showed high selectivity of action towards A(1) receptor and high affinity with K-i values in the low nanomolar range. The pharmacological profile of the most active molecules towards A(1) adenosine receptors was evaluated in cAMP functional assay. Compounds demonstrated their ability to completely counteract the effect of the agonist NECA, thus demonstrating their antagonist profile. Moreover, the most interesting compound, tested in the mouse passive avoidance, exhibited an antiamnesic effect at the doses of 10 and 30 mg/kg. (C) 2014 Published by Elsevier Masson SAS.