Dopamine Receptor Ligands. Part 18: Modification of the Structural Skeleton of Indolobenzazecine-Type Dopamine Receptor Antagonists

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• 作者：Dina Robaa ; Christoph Enzensperger ; Shams El Din Abul Azm ; El Sayeda El Khawass ; Ola El Sayed ; Jochen Lehmann
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：March 25, 2010
• 年：2010
• 卷：53
• 期：6
• 页码：2646-2650
• 全文大小：763K
• 年卷期：v.53,no.6(March 25, 2010)
• ISSN：1520-4804

文摘

On the basis of the D_1/5-selective dopamine antagonist LE 300 (1), an indolo[3,2-f]benzazecine derivative, we changed the annulation pattern of the heterocycles. The target compounds represent novel heterocyclic ring systems. The most constrained indolo[4,3a,3-ef]benzazecine 2 was inactive, but the indolo[4,3a,3-fg]benzazacycloundecene 3 showed antagonistic properties (functional Ca²⁺ assay) with nanomolar affinities (radioligand binding) for all dopamine receptor subtypes, whereas the indolo[2,3-f]benzazecine 4 displayed a selectivity profile similar to 3 but with decreased affinities.