Synthesis and activity of substituted heteroaromatics as positive allosteric modulators for α4β2α5 nicotinic acetylcholine receptors

The design and synthesis of a series of substituted heteroaromatic α4β2α5 positive allosteric modulators is reported. The optimization and development of the heteroaromatic series was carried out from NS9283, and several potent analogues, such as 3-(5-(pyridin-3-yl)-2H-tetrazol-2-yl)benzonitrile (5k...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2014-01, Vol.24 (2), p.674-678
Hauptverfasser:	Jin, Zhuang, Khan, Pasha, Shin, Youseung, Wang, Jingyi, Lin, Li, Cameron, Michael D., Lindstrom, Jon M., Kenny, Paul J., Kamenecka, Theodore M.
Format:	Artikel
Sprache:	eng
Schlagworte:	Allosteric Regulation - drug effects Allosteric Regulation - physiology Animals HEK293 Cells Humans Mice Nicotinic Agonists - chemical synthesis Nicotinic Agonists - pharmacology Nicotinic Antagonists - chemical synthesis Nicotinic Antagonists - pharmacology Oxadiazoles - chemical synthesis Oxadiazoles - pharmacology Positive allosteric modulators Pyridines - chemical synthesis Pyridines - pharmacology Receptors, Nicotinic - physiology Structure-Activity Relationship Substituted heteroaromatics α4β2α5
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Zusammenfassung:	The design and synthesis of a series of substituted heteroaromatic α4β2α5 positive allosteric modulators is reported. The optimization and development of the heteroaromatic series was carried out from NS9283, and several potent analogues, such as 3-(5-(pyridin-3-yl)-2H-tetrazol-2-yl)benzonitrile (5k) and 3,3′-(2H-tetrazole-2,5-diyl)dipyridine (12h) with good in vitro efficacy were discovered.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2013.11.049