Dopamine/Serotonin Receptor Ligands. 16.1 Expanding Dibenz[d,g]azecines to 11- and 12-Membered Homologues. Interaction with Dopamine D1-D5<

详细信息    查看全文

• 作者：Christoph Enzensperger ; Franziska K. U. M&uuml ; ller ; Bä ; rbel Schmalwasser ; Petra Wiecha ; Heidi Traber ; Jochen Lehmann
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：September 6, 2007
• 年：2007
• 卷：50
• 期：18
• 页码：4528 - 4533
• 全文大小：142K
• 年卷期：v.50,no.18(September 6, 2007)
• ISSN：1520-4804

文摘

Oxygenated 7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecines are potent dopamine receptor antagonists,preferentially at D₁/D₅. We synthesized the hydroxylated, methoxylated, and chlorinated 11-membered and12-membered homologues of these 10-membered heterocycles. Their affinities for the human cloned D₁-D₅ receptors (radioligand binding) and functionalities (calcium assay) were measured. Enlarging thedibenzazecines to the corresponding dibenzazacycloundecenes and dibenzazacyclododecenes generallymaintains the high antagonistic affinity for D₁/D₅ but also leads to a compound with a clozapine-like bindingprofile due to additional affinity for D₄.