Carbamoylcholine homologs: synthesis and pharmacology at nicotinic acetylcholine receptors
| Autor: | Bente Frølund, Hans Bräuner-Osborne, Jerzy W. Jaroszewski, Ivan Mikkelsen, Karla Frydenvang, Anders A. Jensen, Povl Krogsgaard-Larsen, Lotte Brehm, Erik Falch |
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| Rok vydání: | 2004 |
| Předmět: |
Pharmacology
Dose-Response Relationship Drug Chemistry Stereochemistry Receptors Nicotinic Cell Line Rats Nicotinic acetylcholine receptor Structure-Activity Relationship Nicotinic agonist Ganglion type nicotinic receptor Biochemistry Muscarinic acetylcholine receptor medicine Animals Humans Carbachol Alpha-4 beta-2 nicotinic receptor Acetylcholine Acetylcholine receptor Cys-loop receptors medicine.drug Protein Binding |
| Zdroj: | European journal of pharmacology. 497(2) |
| ISSN: | 0014-2999 |
| Popis: | In a recent study, racemic 3-(N,N-dimethylamino)butyl-N,N-dimethylcarbamate (1) was shown to be a potent agonist at neuronal nicotinic acetylcholine receptors with a high selectivity for nicotinic over muscarinic acetylcholine receptors [Mol. Pharmacol. 64 (2003) 865-875]. Here we present the synthesis and pharmacological characterization of a series of analogs of, where the methyl group at C-3 has been replaced by different alkyl substituents. Ring systems have been incorporated into the carbon backbone of some of the molecules, or the amino group has been build into ring systems. Furthermore, the (+)- and (-)-enantiomers of have been separated, and X-ray crystallography has revealed that (-)-1 possesses (S)-configuration. The compounds have been characterized pharmacologically at recombinant nicotinic receptor subtypes. The structure-activity relationship study has provided valuable insight into the mode of interactions of and its analogs with neuronal nicotinic acetylcholine receptors. |
| Databáze: | OpenAIRE |
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