Hlasta D J, Luttinger D, Perrone M H, Silbernagel M J, Ward S J, Haubrich D R
J Med Chem. 1987 Sep;30(9):1555-62. doi: 10.1021/jm00392a005.
The synthesis and alpha 2-adrenergic activity of a series of indolin-2-yl and tetrahydroquinolin-2-yl imidazolines are described. The indolin-2-yl imidazoline 4b was found to possess potent alpha 2-adrenergic agonist and antagonist activity. The modification of the substituents on the indoline ring of 4b has led to the separation of these activities. Substitution on the aromatic ring of 4b with halogen or increasing the size of the N-alkyl substituent of 4b gave alpha 2-adrenergic antagonists without agonist activity. The N-allylindoline 4d is more potent than idazoxan in vitro and is equipotent in vivo, but is less receptor selective (alpha 2 vs. alpha 1) than idazoxan. The cis-1,3-dimethylindolin-2-yl imidazoline 6a is an alpha 2-adrenergic agonist equal in potency to clonidine in vitro, while the trans-1,3-dimethylindolin-2-yl imidazoline 6b is a moderately potent alpha 2-adrenergic antagonist.
描述了一系列吲哚啉-2-基和四氢喹啉-2-基咪唑啉的合成及其α2-肾上腺素能活性。发现吲哚啉-2-基咪唑啉4b具有强效α2-肾上腺素能激动剂和拮抗剂活性。对4b吲哚啉环上取代基的修饰导致了这些活性的分离。用卤素取代4b的芳环或增大4b的N-烷基取代基的尺寸可得到无激动剂活性的α2-肾上腺素能拮抗剂。N-烯丙基吲哚啉4d在体外比咪唑克生更有效，在体内效力相当，但与咪唑克生相比，其受体选择性（α2与α1）较低。顺式-1,3-二甲基吲哚啉-2-基咪唑啉6a是一种在体外效力与可乐定相当的α2-肾上腺素能激动剂，而反式-1,3-二甲基吲哚啉-2-基咪唑啉6b是一种中等效力的α2-肾上腺素能拮抗剂。
