57568-79-3Relevant academic research and scientific papers
Synthesis and diuretic activity of alkyl- and arylguanidine analogs of N,N'-dicyclohexyl-4-morpholinecarboxamidine in rats and dogs
Perricone,Humphrey,Skaletzky,Graham,Zandt,Zins
, p. 3693 - 3700 (2007/10/02)
Random screening identified N,N'-dicyclohexyl-4-morpholinecarboxamidine (U-18177, 1) as an orally effective nonkaliuretic diuretic in rats. The diuretic profile of 1 and its 1-adamantyl analog (U-37883A, 4) was confirmed orally in dogs, where they were less potent than standard diuretics but showed furosemide-like natriuresis at ≥100 μmol/kg. However, acute 1 at 61 and 90 μmol/kg iv resulted in lethal cardiac toxicity in dogs. Many analogs of 1 exhibited qualitatively similar diuretic profiles, but none was sufficiently safe to warrant development. Compound 1 also reversed minoxidil's vasodilation in dogs, which led to vascular interaction studies suggesting that analog 4 may block ATP-sensitive K channels. This K channel- blocking mechanism may contribute to the diuretic activity of the series. This is the first report broadly characterizing the diuretic activity of 1 and representative guanidine analogs in rats and dogs and its toxicity and minoxidil-blocking effects in dogs.
Adamantyl containing guanidines
-
, (2008/06/13)
Novel compounds of FIG. 1, pharmaceutical compositions thereof, and systemic means of administration for anti-arrhythmic and diuretic uses are disclosed: STR1
