Decahydrobenzoquinolin-5-one sigma receptor ligands: Divergent development of both sigma 1 and sigma 2 receptor selective examples

详细信息    查看全文

• 作者：Michael C. McLeod ; Jeffrey Aubé ; ¹ ; Kevin J. Frankowski ; ^{kevinf@unc.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Sigma receptor ; CNS ; Decahydroquinoline ; Radioligand binding ; Structure-affinity relationship ; Biology-oriented synthesis
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 December 2016
• 年：2016
• 卷：26
• 期：23
• 页码：5689-5694
• 全文大小：1576 K

文摘

Analogues of the decahydrobenzoquinolin-5-one class of sigma (σ) receptor ligands were used to probe the structure-activity relationship trends for this recently discovered series of σ ligands. In all, 29 representatives were tested for σ and opioid receptor affinity, leading to the identification of compounds possessing improved σ₁ selectivity and, for the first time in this series, examples possessing preferential σ₂ affinity. Several structural features associated with these selectivity trends have been identified. Two analogues of improved selectivity were evaluated in a binding panel of 43 CNS-relevant targets to confirm their sigma receptor preference.