HALOGENATED BIOGENIC AMINES IN BIOCHEMISTRY AND PHARMACOLOGY

生物胺在神经传递、新陈代谢和 对各种生理过程的控制。环卤化类似物有 事实证明，它是研究输运机制的有力工具， 这些胺的储存、释放和作用模式，因为它们模拟 天然化合物的几何构型如此之好。凭借其独特的 体积小，电负性高，氟应该是非常有利的 取代了这些类似物中的氢。几年前，我们开发了 合成这类类似物的新方法，并制备了广泛的 各种生物胺，在不同的环位置带有氟。这个 这些类似物的生物学特性和有用性已被证明 令人意想不到的回报，并继续在大量的 学习。到目前为止，也许最重要的发现是 2-氟肾上腺素是一种纯的β-肾上腺素能激动剂，而 6-氟异构体是一种纯的α-肾上腺素能激动剂。各种解释 因为已经考虑了氟在产生这种特异性中的作用 然后被丢弃。我们现在提出一个临界离子-偶极相互作用 存在于受体上的带正电荷的位置和 苯环上富含电子的碳原子。诱导性撤资 氟会削弱这种相互作用，并产生观察到的 具体细节。氟化环的药代动力学研究结果 邻苯二酚氨基酸展示了它们作为生物示踪剂的潜力， 包括用作18F-Pett扫描剂。在其中的某些类比中， 氟不仅作为放射性示踪剂(18F)，而且还用于 延缓不受欢迎的代谢过程(邻苯二酚甲基化 转移酶)。含氟废水阳极氧化过程中氟的释放 胺和氨基酸推动了将这些化合物作为前体药物的研究。 用于黑色素瘤化疗。

Biogenic amines play key roles in neurotransmission, metabolism, and in control of various physiological processes. Ring-halogenated analogs have proved to be powerful tools for the study of the mechanisms of transport, storage, release, 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 should be a very favorable replacement for hydrogen in these analogs. Some years ago, we developed novel methods for the synthesis of such analogs and have prepared a wide variety of biogenic amines with fluorine at various ring positions. The biological properties and usefulness of these analogs have proved unexpectedly rewarding and continue to find application in a multitude of studies. Perhaps the most significant finding, to date, is that 2-fluoronorepinephrine is a pure beta-adrenergic agonist, while the 6-fluoro isomer is a pure alpha-adrenergic agonist. Various explanations for the role of fluorine in creating such specificity have been considered and discarded. We now propose that a critical ion-dipole interaction exists between a positively-charged site on the receptor and an electron-rich carbon atom of the benzene ring. Inductive withdrawal by fluorine would weaken this interaction and produce the observed specificities. Results from pharmakokinetic studies of ring-fluorinated catechol amino acids demonstrate their potential as biological tracers, including use as 18F-PETT scanning agents. In certain of these analogs, fluorine serves not only as the radioactive tracer (18F), but also to retard an undesirable metabolic process (methylation by catechol-0-methyl transferase). Fluoride release during anodic oxidation of fluorinated amines and amino acids has prompted a study of these compounds as prodrugs for melanoma chemotherapy.