title: Conformational analysis of 6α- and 6β-naltrexol and derivatives and relationship to opioid receptor affinity.
abstract: 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.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Bayron
authors.forename: Amy M
authors.initials: AM
authors.lastname: Deveau
authors.forename: John M
authors.initials: JM
authors.lastname: Stubbs
mesh_terms: D006801:Humans; D008968:Molecular Conformation; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000737:chemistry; D011485:Protein Binding; D011957:Receptors, Opioid / Q000378:metabolism*
chemical_list: D011957:Receptors, Opioid; C010410:6 beta-hydroxynaltrexone; D009271:Naltrexone