Structure-activity relationships for 2-substituted imidazoles as alpha 2-adrenoceptor antagonists.
Several 2-[(1,4-benzodioxan-2-yl)alkyl]imidazoles were prepared and evaluated for their blocking activity and relative selectivity on presynaptic (alpha 2) and postsynaptic (alpha 1) receptors in the isolated rat vas deferens. 1-Ethyl-2-[(1,4-benzodioxan 2-yl)methyl]imidazole (13) was the most selective alpha 2-adrenoceptor antagonist of the series and was, for practical purposes, devoid of alpha 1-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.
D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles