Novel adenosine A1 receptor antagonists. Synthesis and structure–activity relationships of a novel series of 3-(2-cyclohexenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridines Original Research Article

A novel series of 3-(2-cyclohexenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridines was synthesized and evaluated for in vitro adenosine A1 and A2A receptor binding activities. Most of the cyclohexenyl derivatives () were found to be potent adenosine A1 receptor antagonists. In a series of analogues of FR166124 , alcohol , nitrile and amide derivatives ) were found to be more potent A1 antagonists with higher A2A/A1 selectivity than FR166124. Amongst them, showed considerable water solubility (33.3 mg/mL), but lower than that of the sodium salt of FR166124 (>200 mg/mL). Additionally, FR166124 had strong diuretic activity by both p.o. and iv administration in rats (minimum effective dose=0.1 and 0.032 mg/kg, respectively).