The in vitro assays involving investigation of the affinity and selectivity of the newly synthesized imidazoline ligands for alpha₂-adrenoceptors, imidazoline I₁ and imidazoline I₂ binding sites showed very low or no affinity for imidazoline I₂ receptors. 1-[(Imidazolidin-2-yl)imino]indazole (marsanidine), the most active agent at alpha₂-adrenoceptors (K_i = 14 nM), displayed a very high alpha₂/I₁ selectivity ratio = 3879.
The in vivo cardiovascular properties of the selected indazole derivatives of type A were evaluated after intravenous infusion in anaesthetized male Wistar rats. Among the tested compounds the highest hypotensive activity was found for 1-[(imidazolidin-2-yl)imino]-7-methylindazole (Δ MAP = - 43.5 mmHg at dose 10 μg/kg, ED₅₀ = 0.6 mg/kg), which also exhibited a good affinity for alpha₂-adrenoceptors (K_i = 53.5 nM) and moderate affinity for imidazoline I₁ receptors (K_i = 387 nM).
These results suggest that marsanidine may find variety of medicinal uses, especially as an alpha₂-agonist for organoprotection and anaesthesia, while its 7-methyl analogue is a good candidate for further development as a centrally acting antihypertensive drug.

^*This research was supported by the Polish Ministry of Science and Higher Education (Grant N40500532/0458). Sączewski F., Kornicka A., Rybczyńska A., Hudson A.L., Miao S.S., Gdaniec M., Boblewski K., Lehmann A. 1[(Imidazolidin-2-yl)imino]indazole (Marsanidine) – highly alpha₂/I₁ selective agonist: synthesis, X-ray structure and biological activity - accepted for publication in J. Med. Chem. 2008; Sączewski F., Kornicka A., Rybczyńska A., Hudson A.L. Nowe pochodne 1-[(imidazolidyn-2-ylo)imino]indazolu i sposób ich otrzymywania. Patent Application P 383955.

References:
[1] Sączewski F., Kobierska E., Dębowski T., Charakchieva-Minol S., Mokrosz M., Gdaniec M., Nowak S.: Arch. Pharm. Pharm. Med. Chem. 2000, 333, 425-430.
[2] Sączewski F., Hudson A.L., Tyacke R.J., Nutt D.J., Man J., Tabin P., Sączewski J.: Eur. J. Pharm. Sci. 2003, 20, 201-208.
[3] Sączewski F., Tabin P., Tyacke R.J., Maconie A., Sączewski J., Kornicka A., Nutt D.J., Hudson A.L.: Bioorg. Med. Chem. 2006, 14, 6679-6685.

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