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、储藏释放、新陈代谢和 这些胺的作用模式，因为它们模拟了 天然化合物的几何构型如此之好。凭借其 非常小的尺寸和很高的电负性，氟是一种非常 在这些类似物中有利地替代了氢。1970年，我们 开发了将氟引入到 有机分子，并将这些方法应用于 一系列含氟生物胺的合成 不同的环形位置。细菌的生物学特性和用途 这些环氟化生物胺已被证明是 非常有价值，并继续在 大量的研究。也许最重要的发现是， 日期，是6-氟肾上腺素是一种选择性阿尔法- 肾上腺素能激动剂和2-氟肾上腺素是一种选择性β-受体激动剂。 肾上腺素能激动剂。关于氟的作用的各种解释 在创造这种选择性的过程中已经被考虑和抛弃了。 目前正在考虑的建议包括一个关键的偶极子- 苄基羟基与氟之间的偶极斥力 在2位和6位。这种相互作用可能导致侧链 有利于与分子相互作用的构象偏好 分别是β和α肾上腺素能受体。的效果 氟对芳香环电子性质的影响是 在定义选择性方面也被认为是重要的。 区分构象和构象的实验 电子效应已经启动。细菌的生物学特性 包括氟化肾上腺素在内的新类似物具有机械性 意义。

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. Perhaps the most significant finding, to date, is that 6-fluoronorepinephrine is a selective alpha- adrenergic agoinst and 2-fluoronorepinephrine is a selective beta- adrenergic agoinst. Various explanations for the role of fluorine in creating such selectivity have been considered and discarded. Proposals under current consideration include a critical dipole- dipole repulsion between the benzylic hydroxly group and fluorine in the 2- and 6-positions. This interaction could lead to side-chain conformational 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.