SYNTHESIS AND PHARMACOLOGY OF CENTRALLY ACTING DOPAMINE DERIVATIVES AND ANALOGS IN RELATION TO PARKINSONS-DISEASE
SYNTHESIS AND PHARMACOLOGY OF CENTRALLY ACTING DOPAMINE DERIVATIVES AND ANALOGS IN RELATION TO PARKINSONS-DISEASE
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DOI：
10.1021/jm00264a011
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发表时间：
1973-01-01
影响因子：
7.3
通讯作者：
GOODMAN, IJ
中科院分区：
文献类型：
--
作者：
BORGMAN, RJ;MCPHILLIPS, JJ;GOODMAN, IJ
通过选择性O-乙酰化和N-烷基化反应制备了不稳定的、亲脂性的多巴胺衍生物和类似物。建立了合成0，0-二乙酰基多巴胺和3，4-二乙酰氧基-|3-苯基甲胺的选择性O-乙酰化方法。其中几种化合物降低了小鼠的体温，这一反应已被证明是多巴胺能的，其中一种化合物能逆转蛇床子碱诱导的中枢神经系统抑制。因此，结果表明，某些化合物可以穿过血脑屏障，激活中枢神经系统中的多巴胺受体。本研究报道的多巴胺衍生物和类似物旨在穿过血脑屏障，激活中枢神经系统(CNS)中的多巴胺能受体。由于多巴胺(3)和相关的儿茶酚胺显然不能穿过血脑屏障，1有必要设计一种机制来将它们转运到中枢神经系统。
Labile, lipophilic derivatives and analogs of dopamine have beenprepared by selective O-acetylation and N-alkylation procedures. Selective O-acetylation methods for the synthesis of 0, 0-diacetyldopamine and 3, 4-diacetoxy-| 3-phenethylmethylamine were developed. Several of the compounds reduced body temperature in themouse, a response which has beenshown to be dopaminergic, and one caused reversal of re-serpine-induced CNS depression. The results suggest therefore that certain of these compounds cross the blood-brain barrier and activate dopamine receptorsin the CNS.The dopamine derivatives and analogs reportedin this study were designed to cross the blood-brain barrier and activate “dopaminergic” receptors in the central nervous system (CNS). Since dopamine (3) and related catechol-amines evidently do not cross the blood-brain barrier, 1 it is necessary to devise a mechanism for their transport into the CNS.