Abstract
Starting from a known non-specific agonist (1) of nicotinic acetylcholine receptors (nAChRs), rationally guided structural-based design resulted in the discovery of a small series of 5′-phenyl-1,2,5,6-tetrahydro-3,3′-bipyridines (3a–3e) incorporating a phenyl ring off the pyridine core of 1. The compounds were synthesized via successive Suzuki couplings on a suitably functionalized pyridine starting monomer 4 to append phenyl and pyridyl substituents off the 3- and 5-positions, respectively, and then subsequent modifications were made on the flanking pyridyl ring to provide target compounds. Compound 3a is a novel antagonist, which is highly selective for α3β4 nAChR (Ki = 123 nM) over the α4β2 and α7 receptors.
Original language | English |
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Pages (from-to) | 4350-4353 |
Number of pages | 4 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 27 |
Issue number | 18 |
DOIs | |
State | Published - 2017 |
Bibliographical note
Publisher Copyright:© 2017 Elsevier Ltd
Keywords
- Acetylcholine receptor
- Antagonist design
- Nicotine
- Organic synthesis
- Selective antagonist
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry