Chiral Indolo[3,2-f][3]benzazecine-Type Dopamine Receptor Antagonists: Synthesis and Activity of Racemic and Enantiopure Derivatives

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• 作者：Dina Robaa ; Christoph Enzensperger ; Shams ElDin AbulAzm ; Mohamed M. Hefnawy ; Hussein I. El-Subbagh ; Tanveer A. Wani ; Jochen Lehmann
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：October 27, 2011
• 年：2011
• 卷：54
• 期：20
• 页码：7422-7426
• 全文大小：828K
• 年卷期：v.54,no.20(October 27, 2011)
• ISSN：1520-4804

文摘

Racemic and enantiopure 8-substituted derivatives of the lead dopamine receptor antagonist LE 300 (1) were prepared, and their affinities for the dopamine receptors (D₁鈥揇₅) were tested. The separate enantiomers showed significantly different affinities; the (8S)-methyl and (8R)-hyroxymethyl derivatives where the substituents point below the reference plane of the indolo[3,2-f][3]benzazecine scaffold were markedly more active than their enantiomeric counterparts. The racemic 8-carboxy derivative was shown to be selective for the D₅-receptor, even against D₁.