Abstract
A series of tetrakis-azaaromatic quaternary ammonium salts was synthesized to identify compounds with higher affinity and selectivity as antagonists at neuronal nicotinic receptor subtypes (nAChR) that mediate nicotine-evoked DA release. A high hit rate was achieved in identifying potent analogs that inhibit these nAChRs. Three tetrakis analogs, 11j, 11f, and 11g, were identified as potent (IC50 = 3, 28 and 56 nM, respectively) antagonists at these receptors. These compounds represent a novel structural class of nicotinic receptor antagonists.
Original language | English |
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Pages (from-to) | 5753-5757 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 18 |
Issue number | 21 |
DOIs | |
State | Published - Nov 1 2008 |
Bibliographical note
Funding Information:This research was supported by NIH Grant U19DA017548.
Keywords
- Dopamine release
- Nicotine addiction
- Nicotinic acetylcholine receptor
- Quaternary ammonium
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry