The enantiomers of epiboxidine and of two related analogs: Synthesis and estimation of their binding affinity at α4β2 and α7 neuronal nicotinic acetylcholine receptors

被引：7

作者：

Dallanoce, Clelia ^{[1
]}

Matera, Carlo ^{[1
]}

De Amici, Marco ^{[1
]}

Rizzi, Luca ^{[1
]}

Pucci, Luca ^{[2
]}

Gotti, Cecilia ^{[2
]}

Clementi, Francesco ^{[2
]}

De Micheli, Carlo ^{[1
]}

机构：

[1] Univ Milan, Dipartimento Sci Farmaceut Pietro Pratesi, I-20133 Milan, Italy

[2] CNR, Ist Neurosci, I-20133 Milan, Italy

来源：

CHIRALITY | 2012年 / 24卷 / 07期

关键词：

epibatidine; epiboxidine and analogs; neuronal nicotinic acetylcholine receptors; chiral resolution; enantiopure nicotinic ligands; binding affinity; TERT-BUTANESULFINYL IMINES; EPIBATIDINE ISOMERS; REAGENTS; LIGAND;

D O I：

10.1002/chir.22052

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Epiboxidine hydrochlorides (+)-2 and (-)-2, which are the structural analogs of the antipodes of epibatidine (+/-)-1, as well as the enantiomeric pairs (+)-3/(-)-3 and (+)-4/(-)-4 were synthesized and tested for binding affinity at a4 beta 2 and a7 nicotinic acetylcholine receptor (nAChR) subtypes. Final derivatives were prepared through the condensation of racemic N-Boc-7-azabicyclo[2.2.1]heptane-2-one (+/-)-5 with the resolving agent (R)-(+)-2-methyl-2-propanesulfinamide. The pharmacological analysis carried out on the three new enantiomeric pairs evidenced an overall negligible degree of enantioselectivity at both nAChRs subtypes, a result similar to that reported for both natural and unnatural epibatidine enantiomers at the same investigated receptor subtypes. Chirality 24:5435-51, 2012. (C) 2012 Wiley Periodicals, Inc.

引用

页码：543 / 551

页数：9

共 33 条

[31] Epibatidine isomers and analogues: Structure-activity relationships [J].