Conformational Analysis of 6α- and 6β-Naltrexol and Derivatives and Relationship to Opioid Receptor Affinity

Naltrexol and its C6 α and β desoxy, iodo, mesyl, tosyl, trifyl, dimethylcarbamyl, and diphenylcarbamyl derivatives were studied in their energy-minimized C ring chair-like and boat-like conformations using B3LYP/6-31G** and SM5.4/A to estimate aqueous solvation free energy. The results were compare...

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Veröffentlicht in:	Journal of chemical information and modeling 2012-02, Vol.52 (2), p.391-395
Hauptverfasser:	Bayron, Jennifer A, Deveau, Amy M, Stubbs, John M
Format:	Artikel
Sprache:	eng
Schlagworte:	Atomic and molecular physics Calculations and mathematical techniques in atomic and molecular physics (excluding electron correlation calculations) Density-functional theory Electronic structure of atoms, molecules and their ions: theory Exact sciences and technology Humans Molecular Conformation Naltrexone - analogs & derivatives Naltrexone - chemistry Physics Protein Binding Receptors, Opioid - metabolism
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Beschreibung
Zusammenfassung:	Naltrexol and its C6 α and β desoxy, iodo, mesyl, tosyl, trifyl, dimethylcarbamyl, and diphenylcarbamyl derivatives were studied in their energy-minimized C ring chair-like and boat-like conformations using B3LYP/6-31G** and SM5.4/A to estimate aqueous solvation free energy. The results were compared to experimental opioid receptor binding affinities. The total energy difference between β conformers correlated well with MOR binding affinity, while the aqueous solvation free energy correlated well with the KOR binding affinity.
ISSN:	1549-9596 1549-960X
DOI:	10.1021/ci200405u