Enantiomers of 2-[(acylamino)ethyl]-1,4-benzodiazepines, potent ligands of κ-opioid receptor:: Chiral chromatographic resolution, configurational assignment, and biological activity

被引：8

作者：

Azzolina, O

Collina, S

Linati, L

Anzini, M

Cappelli, A

Scheideler, MA

Sbacchi, M

机构：

[1] Univ Pavia, Dipartimento Chim Farmaceut, I-27100 Pavia, Italy

[2] Univ Pavia, Ctr Grandi Strumenti, I-27100 Pavia, Italy

[3] Univ Catanzaro Magna Grecia, Dipartimento Sci Farmacobiol, Catanzaro, Italy

[4] Univ Siena, Dipartimento Farm Chim Tecnol, I-53100 Siena, Italy

[5] SmithKline Beecham, Dept Neurosci, Neurobiol Res, Milan, Italy

来源：

CHIRALITY | 2001年 / 13卷 / 09期

关键词：

tifluadom analogs; opioid receptor ligands; enantiomer separation; semipreparative chiral chromatography; circular dichroism; H-1-COSY; NOESY spectroscopy;

D O I：

10.1002/chir.1185

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Compounds 2a and 3a-e are racemic 2-[(acylamino)ethyl]-1,4-benzodiazepines, tifluadom analogs, with high affinity and selectivity towards the kappa -opioid receptor. We describe the enantiomeric separation of all compounds through liquid chromatography with chiral stationary phases, as well as the resolution of the enantiomers of the most interesting compounds, 2a and 3a, by the semipreparative column Chiralpak AD. The configuration of the resolved enantiomers was investigated: the comparative study of CID and H-1 NMR spectra shows that compounds (-)-2a and (-)-3a have the same absolute configuration of (+)-(S)-tifluadom. A study on the stereoselective interaction with opiate receptors is reported. Chirality 13:606-612, 2001. (C) 2001 Wiley-Liss, Inc.

引用

页码：606 / 612

页数：7

共 19 条

[1] CHIRAL RECOGNITION OF ALKYL 2-ARYLOXYPROPIONATES BY HPLC [J].