Synthesis, Nicotinic Acetylcholine Receptor Binding, and Antinociceptive Properties of 2-exo-2-(2‘-Substituted-3‘-phenyl-5‘-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Novel Nicotinic Antagonist

A series of 2‘-substituted-3‘-phenyl epibatidine analogues were synthesized and evaluated for inhibition of binding at nicotine acetylcholine receptors and for antinociceptive properties in mice. The introduction of a bulky phenyl group at the 3‘-position exerted a profound influence on both recepto...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2001-11, Vol.44 (24), p.4039-4041
Main Authors: Carroll, F. Ivy, Lee, Jeffrey R, Navarro, Hernán A, Brieaddy, Lawrence E, Abraham, Philip, Damaj, M. I, Martin, Billy R
Format: Article
Language:English
Subjects:
Analgesics
Analgesics - chemical synthesis
Analgesics - chemistry
Analgesics - metabolism
Analgesics - pharmacology
Animals
Biological and medical sciences
Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis
Bridged Bicyclo Compounds, Heterocyclic - chemistry
Bridged Bicyclo Compounds, Heterocyclic - metabolism
Bridged Bicyclo Compounds, Heterocyclic - pharmacology
Cerebral Cortex
Cholinergic system
In Vitro Techniques
Male
Medical sciences
Mice
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Nicotinic Antagonists - chemical synthesis
Nicotinic Antagonists - chemistry
Nicotinic Antagonists - metabolism
Nicotinic Antagonists - pharmacology
Pharmacology. Drug treatments
Protein Subunits
Pyridines - chemical synthesis
Pyridines - chemistry
Pyridines - metabolism
Pyridines - pharmacology
Radioligand Assay
Rats
Receptors, Nicotinic - metabolism
Stereoisomerism
Structure-Activity Relationship
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Summary:A series of 2‘-substituted-3‘-phenyl epibatidine analogues were synthesized and evaluated for inhibition of binding at nicotine acetylcholine receptors and for antinociceptive properties in mice. The introduction of a bulky phenyl group at the 3‘-position exerted a profound influence on both receptor binding and antinociceptive effects. Substitution of different groups at the 2‘-position distinguished between agonist and antagonist properties. These results demonstrate that structural requirements for receptor activities and recognition are distinctively different.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm015561v