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

Subtitle:IF 2.661

Abstract: 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. (C) 2010 Elsevier Ltd. All rights reserved.

Publication year:2010

Keywords:Designed multiple ligands, Constrained amino acids, Dual mu/delta opioid antagonists, Organic & medicinal chemistry