Conformational analysis of 2-substituted piperazines
| Autor: | E. Adam Kallel, Daniel Elbaum, Colin Vangel |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
alpha7 Nicotinic Acetylcholine Receptor
Molecular model Pyridines Stereochemistry Clinical Biochemistry Molecular Conformation Pharmaceutical Science Ether Stereoisomerism 010402 general chemistry 01 natural sciences Biochemistry Piperazines chemistry.chemical_compound Drug Discovery medicine Molecular Biology 010405 organic chemistry Chemistry Hydrogen bond Aryl Organic Chemistry Hydrogen Bonding Bridged Bicyclo Compounds Heterocyclic 0104 chemical sciences Molecular Docking Simulation Intramolecular force Epibatidine Molecular Medicine Enantiomer medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 26:3010-3013 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2016.05.022 |
| Popis: | The unusual activity differences of carbon linked versus oxygen linked 2-substituted piperazines as α7 nicotinic acetylcholine receptor agonists led to a conformational study of several examples. The conformational preferences of which are absent from the literature. We report the first study and explanation of the conformational preference of 2-substiturted piperazines and show an example of how this preference controls binding in a pharmaceutically relevant case. In all cases the axial conformation for these 1-acyl and 1 aryl 2-substituted piperazines was found to be preferred. For the ether linked compounds, the axial conformation was found to be further stabilized by an intramolecular hydrogen bond. The axial orientation also places the basic and pyridyl nitrogens into a special orientation that closely mimics nicotine. Molecular modeling studies confirm that the R enantiomers of the compounds can bind to the α7 nicotinic acetylcholine receptor with the basic and pyridyl nitrogens colocalized with their counterparts in Epibatidine. |
| Databáze: | OpenAIRE |
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