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。使用各种合成材料 方法，包括我们开发的新程序，我们有 合成了一系列含氟生物胺 不同的环形位置。由于它的体积很小，高度很高 电负性，氟是氢的一种非常有利的替代品 在这些类似物中。它们的生物学特性和用途 环氟化生物胺已被证明是非常有益的。 并继续在众多研究中找到应用，包括 运输、储存、释放、代谢等机制的研究 以及这些胺的作用方式。特别重要的是 发现6-氟肾上腺素是一种选择性的α-肾上腺素能 激动剂和2-氟肾上腺素是一种选择性β-肾上腺素能 激动剂。解释这些结果的机制包括：1)a) C-F键对激动剂-受体相互作用的直接影响 C-F键对乙醇胺构象的间接影响 侧链。合成的新类似物的检测结果 这些机制表明，电子效应可能更重要。 而不是构象因子。含氟类似物是一种有用的生物 追踪器。例如，[18F]标记的6-氟多胺，生物 6-氟肾上腺素的前体，已被发现是一种极好的 周围去甲肾上腺素能神经支配扫描剂。

Biogenic amines play key roles in neurotransmission, metabolism, and in control of various physiological processes. Using a variety of synthetic methodologies, including novel procedures developed by us, we have prepared a series of biogenic amines with fluorine substituted at various ring-positions. By virtue of its very small size and high electronegativity, fluorine is a very favorable replacement for hydrogen in these analogues. 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, including research on the mechanisms of transport, storage, release, metabolism, and modes of action of these amines. Of particular significance was the discovery that 6-fluoronorepinephrine is a selective alpha-adrenergic agonist and 2-fluoronorepinephrine is a selective beta-adrenergic agonist. Mechanisms considered to explain these results include: 1) a direct effect of the C-F bond on agonist-receptor interaction or 2) an indirect effect of the C-F bond on the conformation of the ethanolamine side-chain. The results of testing of new analogues synthesized to probe these mechanisms indicate that electronic effects may be more important than conformational factors. Fluorinated analogues are useful biological tracers. For example, [18F]-labeled 6-fluorodopamine, the biological precursor to 6-fluoronorepiephrine, has been found to be an excellent scanning agent for peripheral noradrenergic innervation.