Protective effects of FK453, a potent nonxanthine adenosine A1 receptor antagonist, on glycerol-induced acute renal failure in rats

Limits of Ligand Selectivity from Docking to Models: In Silico Screening for A1 Adenosine Receptor Antagonists

“…Its antagonists have been explored as kidney-protective agents, compounds for treating cardiac failure, cognitive enhancers, and antiasthmatic agents [11] , [12] . Structurally diverse antagonists, such as the pyrazolopyridine derivative 2 and the 7-deazaadenine derivative 3 , were previously identified, and some of these compounds were under consideration for clinical use [13] , [14] . The prototypical AR antagonists, i.e.…”

Discovery of 6-Oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)-pyridazinebutanoic Acid (FK 838): A Novel Non-Xanthine Adenosine A1Receptor Antagonist with Potent Diuretic Activity

“…The pyrazolo[1,5- a ]pyridine-based structure of 2 was completely different from known xanthine and non-xanthine adenosine A 1 receptor antagonists, and therefore 2 was a structurally unique adenosine receptor antagonist. Although 2 was a potent diuretic in several species, including humans, the oral bioavailability of 2 was relatively low due to a rapid first-pass effect in the liver and to the poor solubility in water, which also resulted in problems in the preparation of intravenous formulations which are essential for the treatment of acute renal failure, a possible clinical indication for 2 . In addition, 2 was readily converted to the less active cis isomer in solution due to a facile photochemical trans − cis isomerization process 8a…”