Novel tertiary diarylethylamines as functionally selective agonists of the kappa opioid receptor.

• Tác giả: Christopher Baccei, Alexander Broadhead, Austin Chen, Yong Chen, Kym I Lorrain, Matthew R Nelli, Thomas O Schrader, Yu Xue
• Ngôn ngữ: eng
• Thông tin xuất bản: England : Bioorganic & medicinal chemistry letters , 2025
• Bộ sưu tập: NCBI
• ID: 690162

Tóm tắt

Novel kappa opioid receptor (KOR) agonists that preferentially activate G-protein signaling versus β-arrestin-2 recruitment are described. Starting from a literature-reported phenol-containing diphenethylamine KOR agonist, structure-activity relationship (SAR) studies revealed replacement of the phenol with various non-hydroxylated bicyclic heteroaromatics led to tertiary diarylethylamines which retained KOR agonist activity and improved metabolic stability in human liver microsomes. Further optimizations produced compound 39, a potent activator of G-protein signaling (GTPγS EC