Highly potent, non-basic 5-HT₆ ligands. Site mutagenesis evidence for a second binding mode at 5-HT₆ for antagonism

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• 作者：Ralph N. Harris III ; Russel S. Stabler ; David B. Repke ; James M. Kress ; Keith A. Walker ; Renee S. Martin ; Julie M. Brothers ; Mariola Ilnicka ; Simon W. Lee ; Tara Mirzadegan
• 关键词：5-HT6 neutal antagonist ; Non-basic ligands ; Binding model ; 1 ; 6-Disubstituted-tetralins ; Receptor point mutation
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：1 June 2010
• 年：2010
• 卷：20
• 期：11
• 页码：3436-3440
• 全文大小：1001 K

文摘

A series of 5-HT₆ ligands derived from (R)-1-(amino)methyl-6-(phenyl)sulfonyltetralin was prepared that yielded several non-basic analogs having sub-nanomolar affinity. Ligand structure–activity relationships, receptor point mutation studies, and molecular modeling of these novel ligands all combined to reveal a new alternative binding mode to 5-HT₆ for antagonism.