Synthesis and pharmacological properties of 4(5)-(2-ethyl-2,3-dihydro-2 silainden-2-yl)imidazole, a silicon analogue of atipamezole

• Published in: European journal of medicinal chemistry Vol. 31; no. 9; pp. 725 - 729
• Main Authors: Heinonen, P, Sipilä, H, Neuvonen, K, Lönnberg, H, Cockcroft, VB, Wurster, S, Virtanen, R, Savola, MKT, Salonen, JS, Savola, JM
• Format: Journal Article
• Language: English
• Published: PARIS CEDEX 15 Elsevier Masson SAS 1996; Elsevier
• Subjects: adrenergic receptor; atipamezole; Biological and medical sciences; Catecholaminergic system; Chemistry, Medicinal; Grignard reaction; Life Sciences & Biomedicine; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; semi-empirical calculation; silaindane; silaindane; adrenergic receptor; Grignard reaction; atipamezole; semi-empirical calculation; ALPHA-2-ADRENOCEPTORS; BINDING; Human; α2-Adrenergic receptor; Imidazole derivatives; Silicon heterocycle; Rat; Nitrogen heterocycle; Rodentia; In vitro; In vivo; Vertebrata; Biological fixation; Mammalia; Structure activity relation; Animal; Affinity; Subcutaneous administration; Antagonist; Pharmacokinetics; Chemical synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/0223-5234(96)85882-X

4(5)-(2-Ethyl-2,3-dihydro-2-silainden-2-yl)imidazole 2a, 4(5)-(2-methyl-2,3-dihydro-2-silainden-2-yl)imidazole 2b and 4(5)-(2-ethyl-2,3-dihydro-2-silainden-2-yl)-2-methylimidazole 2c, C2 silicon analogues of the commercially available α 2-adrenergic receptor antagonist atipamezole 1, were prepared and their pharmacological properties were evaluated. The results show that 2a retained significant affinity for the receptors, and the in vivo pharmacokinetic properties of 2a were comparable to those of 1.