Hamada A, Yaden E L, Horng J S, Ruffolo R R, Patil P N, Miller D D
J Med Chem. 1985 Sep;28(9):1269-73. doi: 10.1021/jm00147a026.
A series of N-substituted imidazolines and ethylenediamines were synthesized and examined for their activity in alpha- and beta-adrenergic systems. The length of the intermediate side chain between the catechol and imidazoline ring or the amine of the ethylenediamine segment was shown to affect the adrenergic activity. N-[2-(3,4-Dihydroxyphenyl)ethyl]imidazoline hydrochloride (2) and N-[2-(3,4-dihydroxyphenyl)ethyl]ethylenediamine dihydrochloride (4), both with two methylene groups between the catechol and amine segment, were found to be somewhat selective for alpha 2-adrenergic receptors while 1-(3,4-dihydroxybenzyl)imidazoline hydrochloride (1) and N-2-(3,4-dihydroxybenzyl)ethylenediamine dihydrochloride (3), both with one methylene group between the catechol and amine segment, were more selective for alpha1-adrenergic receptors in a pithed rat model. Of the four compounds examined, only compound 2 showed significant direct activity on beta1- and beta2-adrenergic receptors.
合成了一系列N-取代咪唑啉和乙二胺，并检测了它们在α-和β-肾上腺素能系统中的活性。结果表明，儿茶酚和咪唑啉环之间或乙二胺片段的胺之间的中间侧链长度会影响肾上腺素能活性。在去大脑大鼠模型中，儿茶酚和胺片段之间均有两个亚甲基的N-[2-(3,4-二羟基苯基)乙基]咪唑啉盐酸盐（2）和N-[2-(3,4-二羟基苯基)乙基]乙二胺二盐酸盐（4）对α2-肾上腺素能受体具有一定的选择性，而儿茶酚和胺片段之间均有一个亚甲基的1-(3,4-二羟基苄基)咪唑啉盐酸盐（1）和N-2-(3,4-二羟基苄基)乙二胺二盐酸盐（3）对α1-肾上腺素能受体更具选择性。在所检测的四种化合物中，只有化合物2对β1-和β2-肾上腺素能受体表现出显著的直接活性。
