Structure-Activity Relationships for 2-Substituted Imidazoles as α2-Adrenoceptor Antagonists

Article abstract of DOI:10.1021/jm00348a012

Several 2-<(1,4-benzodioxan-2-yl)alkyl>imidazoles were prepared and evaluated for their blocking activity and relative selectivity on presynaptic (α₂) and postsynaptic (α₁) receptors in the isolated rat vas deferens. 1-Ethyl-2-<(1,4-benzodioxan-2-yl)methyl>imidazole (13) was the most selective α₂-adrenoceptor antagonist of the series and was for practical purposes, devoid of α₁-adrenoceptor antagonist activity.The lipophilicity of 13 (log D = 2.31) indicated that it would have an excellent chance to enter the central nervous system.Compound 13 was selected for clinical evaluation as an antidepressant agent.