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，我们已经准备好 一系列不同环上含氟取代的生物胺-- 各就各位。凭借其非常小的尺寸和很高的电负性， 在这些类似物中，氟是氢的一种非常有利的替代品。 这些环-氟生物源的生物学特性和用途 胺已被证明是非常有益的，并继续发现 在众多研究中的应用，包括对 运输、储存、释放、代谢和作用方式的机制 这些胺。具有特别重要意义的是发现6- 氟去甲肾上腺素是一种选择性的α-肾上腺素激动剂和2-肾上腺素受体激动剂。 氟肾上腺素是一种选择性的β-肾上腺素能激动剂。机制 被认为解释这些结果的原因包括：1)C-F的直接影响 激动剂-受体相互作用的键或2)C-F的间接效应 乙醇胺侧链构象上的键。结果是 为探索这些机制而合成的新类似物的测试表明 电子效应可能比构象因素更重要。 氟化类似物是有用的生物示踪剂。例如，[18F]- 标记的6-氟多胺，6-氟多巴胺的生物前体 氟去甲肾上腺素已被发现是一种很好的PET扫描剂 用于外周去甲肾上腺素能神经支配。氟化产品 6-氟肾上腺素、6-氟多巴胺和6-氟多巴的代谢 已经准备好帮助开发这些PET扫描剂。一个 已制备了AZT的二氟亚甲基膦酸类化合物，并发现 积极对抗HIV-逆转转移酶。

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 analogs. The biological properties and usefulness of these ring-flourinated 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-adrenertic 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 analogs sythesized to probe these mechanisms indicate that electronic effects may be more important than conformational factors. Fluorinated analogs are useful biological tracers. For example, [18F]- labeled 6-fluorodopamine, the biological precursor to 6- fluoronorepinephrine, has been found to be an excellent PET-scanning agent for peripheral noradrenergic innervation. Fluorinated products of metabolism of 6-fluoronorepinephrine, 6-fluorodopamine, and 6-fluoro-Dopa have been prepared to aid in development of these PET-scanning agents. A difluoromethylenephosphonate analogue of AZT has been prepared and found to be active against HIV-reverse transciptase.