158366-39-3Relevant academic research and scientific papers
Molecular determinants of ligand binding modes in the histamine H 4 receptor: Linking ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) models to in silico guided receptor mutagenesis studies
Istyastono, Enade P.,Nijmeijer, Saskia,Lim, Herman D.,Van De Stolpe, Andrea,Roumen, Luc,Kooistra, Albert J.,Vischer, Henry F.,De Esch, Iwan J. P.,Leurs, Rob,De Graaf, Chris
experimental part, p. 8136 - 8147 (2012/01/05)
The histamine H4 receptor (H4R) is a G protein-coupled receptor (GPCR) that plays an important role in inflammation. Similar to the homologous histamine H3 receptor (H3R), two acidic residues in the H4/sub
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.
