氯丙嗪与多巴胺：与吩噻嗪类药物抗精神分裂症活性相关的构象相似性。
Chlorpromazine and dopamine: conformational similarities that correlate with the antischizophrenic activity of phenothiazine drugs.
作者信息
Horn A S, Snyder S H
出版信息
Proc Natl Acad Sci U S A. 1971 Oct;68(10):2325-8. doi: 10.1073/pnas.68.10.2325.
Abstract
Phenothiazines and butyrophenones are known to alter dopamine (3,4-dihydroxyphenethylamine) metabolism in the brain in a fashion suggesting that they may block dopamine receptors. We observed, using Dreiding molecular models, that dopamine in its solid-state conformation is superimposable upon a portion of the known x-ray structure of chlorpromazine [2-chloro-10-(3-dimethylaminopropyl)-phenothiazine]. The ability of phenothiazine drugs to mimic the dopamine-like conformation correlates with their antischizophrenic efficacy. These structure-activity relationships explain the importance of a substituent in ring a, a three-carbon side chain bearing the amino group, and a hetero atom between rings a and c.
摘要
已知吩噻嗪类和丁酰苯类药物会以一种表明它们可能阻断多巴胺受体的方式改变大脑中的多巴胺（3,4-二羟基苯乙胺）代谢。我们使用Dreiding分子模型观察到，固态构象的多巴胺与氯丙嗪[2-氯-10-(3-二甲氨基丙基)-吩噻嗪]已知的X射线结构的一部分重叠。吩噻嗪类药物模拟多巴胺样构象的能力与其抗精神分裂症疗效相关。这些构效关系解释了a环中取代基、带有氨基的三碳侧链以及a环和c环之间杂原子的重要性。
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