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Discovery of fused azetidines as novel selective α4β2 neuronal nicotinic receptor (NNR) agonists

✍ Scribed by Ji, Jianguo; Bunnelle, William H.; Li, Tao; Pace, Jennifer M.; Schrimpf, Michael R.; Sippy, Kevin B.; Anderson, David J.; Meyer, Michael D.

Book ID
118189693
Publisher
International Union of Pure and Applied Chemistry
Year
2005
Tongue
English
Weight
201 KB
Volume
77
Category
Article
ISSN
0033-4545

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✦ Synopsis

Abstract

An efficient synthesis of (1__R__,5__S__)-6-(5-cyano-3-pyridinyl)-3,6-diaza-bicyclo[3.2.0]heptane A-366833, a novel potent selective neuronal nicotinic receptor (NNR) agonist, is described. The enantiomerically pure pharmacophore benzyl (1__S__,5__S__)-3,6-diaza-bicyclo[3.2.0]heptane-3-carbamate was successfully constructed from benzyl N-allyl-N-(2-hydroxyimino-ethyl)-carbamate through a convenient approach including an intramolecular [1,3]-dipolar cycloaddition, reductive ring-opening reaction, chiral resolution, and intramolecular cyclization. Subsequent N-arylation of the pharmacophore with 3-bromo-5-cyanopyridine and N-Cbz deprotection with trifluoroacetic acid furnished A-366833.

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A novel series of [3.2.1] azabicyclic bi
A novel series of [3.2.1] azabicyclic biaryl ethers as α3β4 and α6/4β4 nicotinic receptor agonists
✍ John A. Lowe III; Shari L. DeNinno; Jotham W. Coe; Lei Zhang; Scot Mente; Raymon 📂 Article 📅 2010 🏛 Elsevier Science 🌐 English ⚖ 243 KB

We report the synthesis of a series of [3.2.1]azabicyclic biaryl ethers as selective agonists of a3and a6-containing nicotinic receptors. In particular, compound 17a from this series is a potent a3b4 and a6/4b4 receptor agonist in terms of both binding and functional activity. Compound 17a also show