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

页码：1610 / 1613

页数：4

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