DeBernardis J F, Kyncl J J, Basha F Z, Arendsen D L, Martin Y C, Winn M, Kerkman D J
J Med Chem. 1986 Apr;29(4):463-7. doi: 10.1021/jm00154a006.
The synthesis and pharmacology of 2-(5,6-dihydroxy-1,2,3,4-tetrahydro-1-naphthyl)imidazoline (A-54741, 4), a very potent alpha-adrenergic agonist, are described. The change in biological activity resulting from variation of the carbocyclic ring size of 4 from four through seven members (2-5) is presented, as well as an explanation that accounts for this change in activity by considering the "exactness of fit" of these compounds to both the alpha 1- and alpha 2-adrenergic receptors. Compound 4 was found in vitro to be a full agonist with greater potency at the alpha 2 receptor (ED50 norepinephrine (NE)/ED50 4 = 188 +/- 22) than at the alpha 1 receptor (ED50 NE/ED50 4 = 13 +/- 2).
本文描述了一种强效α-肾上腺素能激动剂2-(5,6-二羟基-1,2,3,4-四氢-1-萘基)咪唑啉（A-54741，4）的合成与药理学特性。文中展示了化合物4的碳环大小从四元环到七元环（2-5）变化时生物活性的改变，并通过考虑这些化合物与α1和α2肾上腺素能受体的“契合度”对活性变化做出了解释。体外实验发现化合物4是一种完全激动剂，其对α2受体的效力（ED50去甲肾上腺素（NE）/ED50 4 = 188 ± 22）高于对α1受体的效力（ED50 NE/ED50 4 = 13 ± 2）。
