Abstract
The synthesis and SAR studies about the bicyclic amine, carbamate linker and aromatic ring of a 1,4-diazabicyclo[3.2.2]nonane phenyl carbamate series of alpha7 nAChR agonists is described. The development of the medicinal chemistry strategy and SAR which led to the identification of 5 and 7aa as subtype selective, high affinity alpha7 agonists as excellent leads for further evaluation is discussed, along with key physicochemical and pharmacokinetic data highlighting their lead potential.
MeSH terms
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Animals
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Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
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Bridged Bicyclo Compounds, Heterocyclic / chemistry
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Bridged Bicyclo Compounds, Heterocyclic / pharmacokinetics
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Carbamates / chemical synthesis*
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Carbamates / chemistry
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Carbamates / pharmacokinetics
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Cell Line
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Humans
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Male
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Nicotinic Agonists / chemical synthesis*
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Nicotinic Agonists / chemistry
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Nicotinic Agonists / pharmacokinetics
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Phenylcarbamates / chemical synthesis*
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Phenylcarbamates / chemistry
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Phenylcarbamates / pharmacokinetics
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Rats
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Rats, Sprague-Dawley
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Receptors, Nicotinic / chemistry*
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Receptors, Nicotinic / metabolism
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Structure-Activity Relationship
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alpha7 Nicotinic Acetylcholine Receptor
Substances
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1,4-diazabicyclo(3.2.2)nonane phenyl carbamate
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Bridged Bicyclo Compounds, Heterocyclic
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Carbamates
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Chrna7 protein, human
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Chrna7 protein, rat
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Nicotinic Agonists
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Phenylcarbamates
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Receptors, Nicotinic
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alpha7 Nicotinic Acetylcholine Receptor