We developed a procedure to synthesize a series of N-alkyl-2-methoxy-11-hydroxynoraporphines from thebaine and evaluated their binding affinities at dopamine D1 and D2 receptors in rat forebrain tissue. At D2 receptors, the most potent 10,11-catechol-aporphine was (R)-(-)-2-methoxy-N-n-propylnorapomorphine (D2, Ki = 1.3 nM; D1, Ki = 6450 nM), and the most selective and potent 11-monohydroxy aporphine was (R)-(-)-2-methoxy-11-hydroxy-N-n-propylnoraporphine (D2, Ki = 44 nM; D1, Ki = 1690 nM). In contrast, the N-methyl congeners (R)-(-)-2-methoxy-11-hydroxy-N-methyl-aporphine (D1 vs D2, Ki = 46 vs 235 nM) showed higher D1 than D2 affinity, indicating that N-alkyl substituents have major effects on D2 affinity and D2/D1 selectivity in such 2-methoxy-11-monohydroxy-substituted aporphines.

中文翻译：

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N-烷基-11-羟基-2-甲氧基Noraporphines的合成和多巴胺受体亲和力：N-烷基取代基决定D1对D2受体的选择性。

我们开发了一种从蒂巴因合成一系列N-烷基-2-甲氧基-11-羟基Noraporphiphines的程序，并评估了它们在大鼠前脑组织中对多巴胺D1和D2受体的结合亲和力。在D2受体上，最有效的10,11-邻苯二酚-吗啡是（R）-（-）-2-甲氧基-Nn-丙基去甲吗啡碱（D2，Ki = 1.3 nM; D1，Ki = 6450 nM），且选择性最高和有效的11-单羟基阿菲啡是（R）-（-）-2-甲氧基-11-羟基-Nn-丙基诺拉啡（D2，Ki = 44 nM; D1，Ki = 1690 nM）。相比之下，N-甲基同类物（R）-（-）-2-甲氧基-11-羟基-N-甲基-Aporphine（D1 vs D2，Ki = 46 vs 235 nM）显示D1高于D2亲和力，表明在这样的2-甲氧基-11-单羟基取代的卟啉中，N-烷基取代基对D2亲和力和D2 / D1选择性具有重大影响。