HALOGENATED BIOGENIC AMINES IN BIOCHEMISTRY AND PHARMACOLOGY

生物胺在神经传递、新陈代谢、 并控制各种生理过程。戒指- 氟化类似物已被证明是研究的有力工具 运输、储存、释放、新陈代谢和 这些胺的作用模式，因为它们模拟几何构型 对天然化合物的了解如此之好。由于它的体积很小 且电负性高，氟是一种非常有利的 取代了这些类似物中的氢。1970年，我们开发了 将氟引入有机材料的新方法 分子，并已将这些方法应用于合成广泛的 各种生物胺，在不同的环位置上有氟。 这些环-氟化化合物的生物学特性和用途 生物胺已被证明是非常有价值的，并将继续 在众多研究中找到应用。特别的 重要的是发现6-氟肾上腺素是一种 选择性α-肾上腺素能激动剂和2-氟肾上腺素 一种选择性的β肾上腺素能激动剂。对这一现象的各种解释 氟在产生这种选择性中的作用一直是 被考虑过，但被抛弃了。目前正在审议的提案 包括一种临界偶极-偶极斥力 羟基和氟在2位和6位。这 相互作用可能导致侧链构象偏好 有利于与β和α肾上腺素能相互作用 分别是受体。氟对电子元器件的影响 芳香环的性质也被认为是重要的 在定义选择性方面。区分不同的实验 构象效应和电子效应已经启动。 新型类似物的生物学特性，包括氟化 肾上腺素具有机械学意义。18F-标记物的使用 6-氟多胺，6-氟多胺的生物前体 氟去甲肾上腺素已被发现是一种很好的扫描方法 外周去甲肾上腺素能神经支配药。

Biogenic amines play key roles in neurotransmission, metabolism, and in control of various physiological processes. Ring- fluorinated analogs have proved to be powerful tools for the study of the mechanisms of transport, storage, release, metabolism, and modes of action of these amines since they simulate the geometries of the natural compounds so well. By virtue of its very small size and high electronegativity, fluorine is a very favorable replacement for hydrogen in these analogs. In 1970, we developed novel methods for the introduction of fluorine into organic molecules and have applied these methods to the syntheses of a wide variety of biogenic amines with fluorine at various ring-positions. The biological properties and usefulness of these ring-fluorinated biogenic amines have proved to be extremely rewarding and continue to find applications in a multitude of studies. Of particular significance was the discovery that 6-fluoronorepinephrine is a selective alpha-adrenergic agonist and 2-fluoronorepinephrine is a selective beta-adrenergic agonist. Various explanations for the role of fluorine in creating such selectivities have been considered and discarded. Proposals under current consideration include a critical dipole-dipole repulsion between the benzylic hydroxyl group and fluorine in the 2- and 6-positions. This interaction could lead to side-chain conformation preferences favorable for interaction with the beta and alpha adrenergic receptors, respectively. Effects of fluorine on the electronic properties of the aromatic ring are considered also to be important in defining selectivities. Experiments to differentiate between conformational and electronic effects have been initiated. Biological properties of new analogs, including fluorinated epinephrines have mechanistic significance. The use of 18F-labeled 6-fluorodopamine, the biological precursor to 6- fluoronorepinephrine, has been found to be an excellent scanning agent for peripheral noradrenergic innervation.