Novel multiple opioid ligands based on 4-aminobenzazepinone (Aba), azepinoindole (Aia) and tetrahydroisoquinoline (Tic) scaffolds

作者：Ballet Steven^*; Marczak Ewa D; Feytens Debby; Salvadori Severo; Sasaki Yusuke; Abell Andrew D; Lazarus Lawrence H; Balboni Gianfranco; Tourwe Dirk

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(5): 1610-1613.

DOI：10.1016/j.bmcl.2010.01.055

• Designed multiple ligands
• Constrained amino acids
• Dual mu/delta opioid antagonists

The dimerization and trimerization of the Dmt-Tic, Dmt-Aia and Dmt-Aba pharmacophores provided multiple ligands which were evaluated in vitro for opioid receptor binding and functional activity. Whereas the Tic-and Aba multimers proved to be dual and balanced delta/mu antagonists, as determined by the functional [S(35)] GTP gamma S binding assay, the dimerization of potent Aia-based 'parent' ligands unexpectedly resulted in substantial less efficient receptor binding and non-active dimeric compounds.

• 出版日期2010-3-1