3-[(Imidazolidin-2-yl)imino]indazole ligands with selectivity for the α2-adrenoceptor compared to the imidazoline I1 receptor

The effect of 7-fluoro-marsanidine, a novel α2-adrenoceptor agonist, on extracellular noradrenaline in rat frontal cortex: A microdialysis study

“…This further suggests marsanidine and 7-fluoro-marsanidine were able to exert their sedative effects probably at the level of LC. Future studies will investigate the nature and duration of sedation exerted by these new drugs; however, this observation supports ours and others' previous findings that these ligands are potent ␣ 2 -AR agonists [35,43]. Given that the drugs were administered in the rats peripherally via i.p.…”

“…However marsanidine, exerted its inhibitory effect to a lesser extent on NA release when compared to 7-fluoro-marsanidine at the same dose of 1 mg/kg. One possible explanation for the weaker effect of marsanidine is that as seen in previous experiments marsanidine is a partial agonist, but further experiments would need to be performed to confirm this [35].…”

“…Our group has recently evaluated a series of fluorinated derivatives of marsanidine (1) and its methylene analogue (2) (Fig. 1) [42], both of which were previously shown to be highly selective partial ␣ 2 -AR agonists [34][35][36]. Preliminary in vitro radioligand binding assays in rat brain and kidney membranes identified 7-fluoro-1-[(imidazolidin-2-yl) imino]-1H-indazole or 7-fluoro-marsanidine (1a, Fig.…”

“…Ligands acting as agonists and antagonists at these receptors thus have a wide variety of therapeutic application in both human and animals [13]. Three subtypes of ␣ 2 -AR have been identified [29]: ␣ 2A , ␣ 2B , and ␣ 2C , of which ␣ 2A -AR are the predominant subtype found in the brain [ (1) and its methylene analogue (2) [33,35]. 1a represents the 7-fluoro derivative of marsanidine under investigation in the current study.…”

1‐[(Imidazolidin‐2‐yl)imino]‐1H‐indoles as new hypotensive agents: synthesis and in vitro and in vivo biological studies

“…Compounds 3a–i were obtained according to the method described by Sączewski et al . A solution of the appropriate 1‐amino‐1 H ‐indole ( 2a–i ) (4.6 mmol) and N ‐ tert ‐butoxycarbonyl‐2‐methylthio‐4,5‐dihydro‐1 H ‐imidazole (1.1 g, 5.1 mmol) in acetic acid (3 mL) was stirred at 62–65 °C (oil bath) for 16 h. Then, the solvent was evaporated under reduced pressure, and the oily residue was treated with water (7 mL).…”