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

被引：6
作者：
Ballet, Steven [1 ,2 ]
Marczak, Ewa D. [3 ]
Feytens, Debby [1 ]
Salvadori, Severo [4 ,5 ]
Sasaki, Yusuke [6 ]
Abell, Andrew D. [2 ]
Lazarus, Lawrence H. [3 ]
Balboni, Gianfranco [7 ]
Tourwe, Dirk [1 ]
机构：
[1] Vrije Univ Brussels, Dept Organ Chem, B-1050 Brussels, Belgium
[2] Univ Adelaide, Sch Chem & Phys, Adelaide, SA 5005, Australia
[3] Natl Inst Environm Hlth Sci, Med Chem Grp, LP, Res Triangle Pk, NC 27709 USA
[4] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy
[5] Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy
[6] Tohoku Pharmaceut Univ, Dept Pharmacol, Aoba Ku, Sendai, Miyagi 9818558, Japan
[7] Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 05期
基金：
澳大利亚研究理事会;
关键词：
Designed multiple ligands; Constrained amino acids; Dual mu/delta opioid antagonists; RECEPTOR ANTAGONISTS; BIVALENT LIGANDS; DOUBLE-ENKEPHALINS; SIDE-CHAIN; ANALOGS; AGONISTS; PHARMACOPHORE; PEPTIDE; POTENT; BINALTORPHIMINE;
D O I：
10.1016/j.bmcl.2010.01.055
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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.
引用
收藏
页码：1610 / 1613
页数：4
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