The crystal structure and molecular conformation of threo 5-methylmetadone in relation to opioid receptor binding
W. L. Duax, G. D. Smith, J. F. Griffin, P. D. Strong, P. S. Portoghese
Crystals of the hydrochloride salt of the biologically inactive threo isomer of 5-methylmethadone, C22H30ONCl, are monoclinic space group P21 with unit cell dimnsionsa = 11.019 Å, b = 8.6153Å, c = 10.680Å and β = 93.026°. The observed conformation is one in which the nitrogen bearing chain is extended with the substituents on C(5) and C(6) nearly eclipsed, a feature compatible with NMR studies and molecular mechanics calculations. The very potent agonist (5S, 6S)-erythro-5-methylmethadone has a solid state conformation in which the N atom is rotated back toward the phenyl rings [C(4)-C(5)-C(6)-N = 97°]in agreement with molecular mechanics calculations. The fact that the more potent enantiomers, (6R)-methadone and (5S)-isomethadone, and the inactive threo isomer are observed in the extended solid state conformation in contrast to (5S, 6S)-erythro-5-methylmethadone is consistent with three different models for their interaction with opioid receptors. It is proposed that the more likely of these involves a receptor bound conformation of (6R)-methadone and (5S)-isomethadone that resembles the conformation of (5S, 6S)-erythro-5-methylmethadone or that opioid receptors recognize both gauche-like and extended conformations.
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5-methylmethadone Medicine & Life Sciences
Molecular Conformation Medicine & Life Sciences
Crystal structure Chemical Compounds
Conformations Chemical Compounds
isomethadone Medicine & Life Sciences
Molecular mechanics Chemical Compounds
Mechanics Medicine & Life Sciences
Methadone Chemical Compounds
Duax, W. L., Smith, G. D., Griffin, J. F., Strong, P. D., & Portoghese, P. S. (1984). The crystal structure and molecular conformation of threo 5-methylmetadone in relation to opioid receptor binding. Tetrahedron, 40(3), 467-471. https://doi.org/10.1016/0040-4020(84)85051-6
The crystal structure and molecular conformation of threo 5-methylmetadone in relation to opioid receptor binding. / Duax, W. L.; Smith, G. D.; Griffin, J. F.; Strong, P. D.; Portoghese, P. S.
In: Tetrahedron, Vol. 40, No. 3, 1984, p. 467-471.
Duax, WL, Smith, GD, Griffin, JF, Strong, PD & Portoghese, PS 1984, 'The crystal structure and molecular conformation of threo 5-methylmetadone in relation to opioid receptor binding', Tetrahedron, vol. 40, no. 3, pp. 467-471. https://doi.org/10.1016/0040-4020(84)85051-6
Duax WL, Smith GD, Griffin JF, Strong PD, Portoghese PS. The crystal structure and molecular conformation of threo 5-methylmetadone in relation to opioid receptor binding. Tetrahedron. 1984;40(3):467-471. https://doi.org/10.1016/0040-4020(84)85051-6
Duax, W. L. ; Smith, G. D. ; Griffin, J. F. ; Strong, P. D. ; Portoghese, P. S. / The crystal structure and molecular conformation of threo 5-methylmetadone in relation to opioid receptor binding. In: Tetrahedron. 1984 ; Vol. 40, No. 3. pp. 467-471.
@article{118f3060c92544cca3e6a31d5936f872,
title = "The crystal structure and molecular conformation of threo 5-methylmetadone in relation to opioid receptor binding",
abstract = "Crystals of the hydrochloride salt of the biologically inactive threo isomer of 5-methylmethadone, C22H30ONCl, are monoclinic space group P21 with unit cell dimnsionsa = 11.019 {\AA}, b = 8.6153{\AA}, c = 10.680{\AA} and β = 93.026°. The observed conformation is one in which the nitrogen bearing chain is extended with the substituents on C(5) and C(6) nearly eclipsed, a feature compatible with NMR studies and molecular mechanics calculations. The very potent agonist (5S, 6S)-erythro-5-methylmethadone has a solid state conformation in which the N atom is rotated back toward the phenyl rings [C(4)-C(5)-C(6)-N = 97°]in agreement with molecular mechanics calculations. The fact that the more potent enantiomers, (6R)-methadone and (5S)-isomethadone, and the inactive threo isomer are observed in the extended solid state conformation in contrast to (5S, 6S)-erythro-5-methylmethadone is consistent with three different models for their interaction with opioid receptors. It is proposed that the more likely of these involves a receptor bound conformation of (6R)-methadone and (5S)-isomethadone that resembles the conformation of (5S, 6S)-erythro-5-methylmethadone or that opioid receptors recognize both gauche-like and extended conformations.",
author = "Duax, {W. L.} and Smith, {G. D.} and Griffin, {J. F.} and Strong, {P. D.} and Portoghese, {P. S.}",
journal = "Tetrahedron",
T1 - The crystal structure and molecular conformation of threo 5-methylmetadone in relation to opioid receptor binding
AU - Duax, W. L.
AU - Smith, G. D.
AU - Griffin, J. F.
AU - Strong, P. D.
AU - Portoghese, P. S.
N2 - Crystals of the hydrochloride salt of the biologically inactive threo isomer of 5-methylmethadone, C22H30ONCl, are monoclinic space group P21 with unit cell dimnsionsa = 11.019 Å, b = 8.6153Å, c = 10.680Å and β = 93.026°. The observed conformation is one in which the nitrogen bearing chain is extended with the substituents on C(5) and C(6) nearly eclipsed, a feature compatible with NMR studies and molecular mechanics calculations. The very potent agonist (5S, 6S)-erythro-5-methylmethadone has a solid state conformation in which the N atom is rotated back toward the phenyl rings [C(4)-C(5)-C(6)-N = 97°]in agreement with molecular mechanics calculations. The fact that the more potent enantiomers, (6R)-methadone and (5S)-isomethadone, and the inactive threo isomer are observed in the extended solid state conformation in contrast to (5S, 6S)-erythro-5-methylmethadone is consistent with three different models for their interaction with opioid receptors. It is proposed that the more likely of these involves a receptor bound conformation of (6R)-methadone and (5S)-isomethadone that resembles the conformation of (5S, 6S)-erythro-5-methylmethadone or that opioid receptors recognize both gauche-like and extended conformations.
AB - Crystals of the hydrochloride salt of the biologically inactive threo isomer of 5-methylmethadone, C22H30ONCl, are monoclinic space group P21 with unit cell dimnsionsa = 11.019 Å, b = 8.6153Å, c = 10.680Å and β = 93.026°. The observed conformation is one in which the nitrogen bearing chain is extended with the substituents on C(5) and C(6) nearly eclipsed, a feature compatible with NMR studies and molecular mechanics calculations. The very potent agonist (5S, 6S)-erythro-5-methylmethadone has a solid state conformation in which the N atom is rotated back toward the phenyl rings [C(4)-C(5)-C(6)-N = 97°]in agreement with molecular mechanics calculations. The fact that the more potent enantiomers, (6R)-methadone and (5S)-isomethadone, and the inactive threo isomer are observed in the extended solid state conformation in contrast to (5S, 6S)-erythro-5-methylmethadone is consistent with three different models for their interaction with opioid receptors. It is proposed that the more likely of these involves a receptor bound conformation of (6R)-methadone and (5S)-isomethadone that resembles the conformation of (5S, 6S)-erythro-5-methylmethadone or that opioid receptors recognize both gauche-like and extended conformations.
JO - Tetrahedron
JF - Tetrahedron