Caroon J M, Clark R D, Kluge A F, Olah R, Repke D B, Unger S H, Michel A D, Whiting R L
J Med Chem. 1982 Jun;25(6):666-70. 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 (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.
制备了几种2-[(1,4-苯并二恶烷-2-基)烷基]咪唑，并评估了它们对离体大鼠输精管中突触前（α2）和突触后（α1）受体的阻断活性和相对选择性。1-乙基-2-[(1,4-苯并二恶烷-2-基)甲基]咪唑（13）是该系列中最具选择性的α2肾上腺素能受体拮抗剂，实际上它没有α1肾上腺素能受体拮抗剂活性。13的亲脂性（log D = 2.31）表明它有很好的机会进入中枢神经系统。化合物13被选作抗抑郁药进行临床评估。
