The Experts below are selected from a list of 30 Experts worldwide ranked by ideXlab platform
Giuseppe Pappalardo - One of the best experts on this subject based on the ideXlab platform.
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x ray molecular structures and theoretical conformational studies of narcotic analgesics α n cis 3 chloroallyl normetazocine ethylKetazocine and Ketazocine
Journal of Pharmaceutical Sciences, 1993Co-Authors: Giuliano Bandoli, Antonio Grassi, Giuseppe PappalardoAbstract:The X-ray molecular structures of the narcotic analgesics α-(-)-2-cis-3-chlorallyl-2’-hydroxy-5,9-dimethyl-6,7-benzomorphan (1) and α-(±)-2-cyclopropylmethyl-2’-hydroxy-5-ethyl-9-methyl-8-oxo- 6,7-benzomorphan (ethylKetazocine, 2) were determined. The structures and conformations in the crystal were compared and discussed with respect to that of α-(±)-2-cyclopropylmethyl-2’-hydroxy-5,9-dimethyl-8- oxo-6,7-benzomorfan (Ketazocine, 3) and those of 15 analogous compounds of the 2’-hydroxy-6,7-benzomorphan series whose structures were previously determined by X-ray analysis. Molecular modeling routines for 1, 2, and 3 produced configurations (N-equatorial) and conformations (distorted chair) of the piperidine ring that were in agreement with those found in the solids. Theoretical studies of the conformations and the rotational energetics of 1, 2, and 3 as cationic species were performed by both the force field (MM2) and the semi- quantltatlve (AM1) methods. The latter method predicted three low energy conformations about N—C(12) and C(12)—C(13) bonds, one of these being more significantly populated (60-68%). The AM1 results were not reproduced by the MM2 method, which predicted four low energy conformations. An interesting common feature of 1,2, and 3 that was noted with both methods was the restricted interconversion route from the conformational state to another through rotations about the C(12)—C(13) bond. The conformational results were discussed in terms of a working hypothesis for regulation of relative p. and « analgesic activities of benzomorphans.
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X-ray Molecular Structures and Theoretical Conformational Studies of Narcotic Analgesics α(—)-N-cis-3-Chloroallyl- normetazocine, EthylKetazocine, and Ketazocine
Journal of pharmaceutical sciences, 1993Co-Authors: Giuliano Bandoli, Antonio Grassi, Giuseppe PappalardoAbstract:The X-ray molecular structures of the narcotic analgesics α-(-)-2-cis-3-chlorallyl-2’-hydroxy-5,9-dimethyl-6,7-benzomorphan (1) and α-(±)-2-cyclopropylmethyl-2’-hydroxy-5-ethyl-9-methyl-8-oxo- 6,7-benzomorphan (ethylKetazocine, 2) were determined. The structures and conformations in the crystal were compared and discussed with respect to that of α-(±)-2-cyclopropylmethyl-2’-hydroxy-5,9-dimethyl-8- oxo-6,7-benzomorfan (Ketazocine, 3) and those of 15 analogous compounds of the 2’-hydroxy-6,7-benzomorphan series whose structures were previously determined by X-ray analysis. Molecular modeling routines for 1, 2, and 3 produced configurations (N-equatorial) and conformations (distorted chair) of the piperidine ring that were in agreement with those found in the solids. Theoretical studies of the conformations and the rotational energetics of 1, 2, and 3 as cationic species were performed by both the force field (MM2) and the semi- quantltatlve (AM1) methods. The latter method predicted three low energy conformations about N—C(12) and C(12)—C(13) bonds, one of these being more significantly populated (60-68%). The AM1 results were not reproduced by the MM2 method, which predicted four low energy conformations. An interesting common feature of 1,2, and 3 that was noted with both methods was the restricted interconversion route from the conformational state to another through rotations about the C(12)—C(13) bond. The conformational results were discussed in terms of a working hypothesis for regulation of relative p. and « analgesic activities of benzomorphans.
Giuliano Bandoli - One of the best experts on this subject based on the ideXlab platform.
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x ray molecular structures and theoretical conformational studies of narcotic analgesics α n cis 3 chloroallyl normetazocine ethylKetazocine and Ketazocine
Journal of Pharmaceutical Sciences, 1993Co-Authors: Giuliano Bandoli, Antonio Grassi, Giuseppe PappalardoAbstract:The X-ray molecular structures of the narcotic analgesics α-(-)-2-cis-3-chlorallyl-2’-hydroxy-5,9-dimethyl-6,7-benzomorphan (1) and α-(±)-2-cyclopropylmethyl-2’-hydroxy-5-ethyl-9-methyl-8-oxo- 6,7-benzomorphan (ethylKetazocine, 2) were determined. The structures and conformations in the crystal were compared and discussed with respect to that of α-(±)-2-cyclopropylmethyl-2’-hydroxy-5,9-dimethyl-8- oxo-6,7-benzomorfan (Ketazocine, 3) and those of 15 analogous compounds of the 2’-hydroxy-6,7-benzomorphan series whose structures were previously determined by X-ray analysis. Molecular modeling routines for 1, 2, and 3 produced configurations (N-equatorial) and conformations (distorted chair) of the piperidine ring that were in agreement with those found in the solids. Theoretical studies of the conformations and the rotational energetics of 1, 2, and 3 as cationic species were performed by both the force field (MM2) and the semi- quantltatlve (AM1) methods. The latter method predicted three low energy conformations about N—C(12) and C(12)—C(13) bonds, one of these being more significantly populated (60-68%). The AM1 results were not reproduced by the MM2 method, which predicted four low energy conformations. An interesting common feature of 1,2, and 3 that was noted with both methods was the restricted interconversion route from the conformational state to another through rotations about the C(12)—C(13) bond. The conformational results were discussed in terms of a working hypothesis for regulation of relative p. and « analgesic activities of benzomorphans.
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X-ray Molecular Structures and Theoretical Conformational Studies of Narcotic Analgesics α(—)-N-cis-3-Chloroallyl- normetazocine, EthylKetazocine, and Ketazocine
Journal of pharmaceutical sciences, 1993Co-Authors: Giuliano Bandoli, Antonio Grassi, Giuseppe PappalardoAbstract:The X-ray molecular structures of the narcotic analgesics α-(-)-2-cis-3-chlorallyl-2’-hydroxy-5,9-dimethyl-6,7-benzomorphan (1) and α-(±)-2-cyclopropylmethyl-2’-hydroxy-5-ethyl-9-methyl-8-oxo- 6,7-benzomorphan (ethylKetazocine, 2) were determined. The structures and conformations in the crystal were compared and discussed with respect to that of α-(±)-2-cyclopropylmethyl-2’-hydroxy-5,9-dimethyl-8- oxo-6,7-benzomorfan (Ketazocine, 3) and those of 15 analogous compounds of the 2’-hydroxy-6,7-benzomorphan series whose structures were previously determined by X-ray analysis. Molecular modeling routines for 1, 2, and 3 produced configurations (N-equatorial) and conformations (distorted chair) of the piperidine ring that were in agreement with those found in the solids. Theoretical studies of the conformations and the rotational energetics of 1, 2, and 3 as cationic species were performed by both the force field (MM2) and the semi- quantltatlve (AM1) methods. The latter method predicted three low energy conformations about N—C(12) and C(12)—C(13) bonds, one of these being more significantly populated (60-68%). The AM1 results were not reproduced by the MM2 method, which predicted four low energy conformations. An interesting common feature of 1,2, and 3 that was noted with both methods was the restricted interconversion route from the conformational state to another through rotations about the C(12)—C(13) bond. The conformational results were discussed in terms of a working hypothesis for regulation of relative p. and « analgesic activities of benzomorphans.
Antonio Grassi - One of the best experts on this subject based on the ideXlab platform.
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x ray molecular structures and theoretical conformational studies of narcotic analgesics α n cis 3 chloroallyl normetazocine ethylKetazocine and Ketazocine
Journal of Pharmaceutical Sciences, 1993Co-Authors: Giuliano Bandoli, Antonio Grassi, Giuseppe PappalardoAbstract:The X-ray molecular structures of the narcotic analgesics α-(-)-2-cis-3-chlorallyl-2’-hydroxy-5,9-dimethyl-6,7-benzomorphan (1) and α-(±)-2-cyclopropylmethyl-2’-hydroxy-5-ethyl-9-methyl-8-oxo- 6,7-benzomorphan (ethylKetazocine, 2) were determined. The structures and conformations in the crystal were compared and discussed with respect to that of α-(±)-2-cyclopropylmethyl-2’-hydroxy-5,9-dimethyl-8- oxo-6,7-benzomorfan (Ketazocine, 3) and those of 15 analogous compounds of the 2’-hydroxy-6,7-benzomorphan series whose structures were previously determined by X-ray analysis. Molecular modeling routines for 1, 2, and 3 produced configurations (N-equatorial) and conformations (distorted chair) of the piperidine ring that were in agreement with those found in the solids. Theoretical studies of the conformations and the rotational energetics of 1, 2, and 3 as cationic species were performed by both the force field (MM2) and the semi- quantltatlve (AM1) methods. The latter method predicted three low energy conformations about N—C(12) and C(12)—C(13) bonds, one of these being more significantly populated (60-68%). The AM1 results were not reproduced by the MM2 method, which predicted four low energy conformations. An interesting common feature of 1,2, and 3 that was noted with both methods was the restricted interconversion route from the conformational state to another through rotations about the C(12)—C(13) bond. The conformational results were discussed in terms of a working hypothesis for regulation of relative p. and « analgesic activities of benzomorphans.
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X-ray Molecular Structures and Theoretical Conformational Studies of Narcotic Analgesics α(—)-N-cis-3-Chloroallyl- normetazocine, EthylKetazocine, and Ketazocine
Journal of pharmaceutical sciences, 1993Co-Authors: Giuliano Bandoli, Antonio Grassi, Giuseppe PappalardoAbstract:The X-ray molecular structures of the narcotic analgesics α-(-)-2-cis-3-chlorallyl-2’-hydroxy-5,9-dimethyl-6,7-benzomorphan (1) and α-(±)-2-cyclopropylmethyl-2’-hydroxy-5-ethyl-9-methyl-8-oxo- 6,7-benzomorphan (ethylKetazocine, 2) were determined. The structures and conformations in the crystal were compared and discussed with respect to that of α-(±)-2-cyclopropylmethyl-2’-hydroxy-5,9-dimethyl-8- oxo-6,7-benzomorfan (Ketazocine, 3) and those of 15 analogous compounds of the 2’-hydroxy-6,7-benzomorphan series whose structures were previously determined by X-ray analysis. Molecular modeling routines for 1, 2, and 3 produced configurations (N-equatorial) and conformations (distorted chair) of the piperidine ring that were in agreement with those found in the solids. Theoretical studies of the conformations and the rotational energetics of 1, 2, and 3 as cationic species were performed by both the force field (MM2) and the semi- quantltatlve (AM1) methods. The latter method predicted three low energy conformations about N—C(12) and C(12)—C(13) bonds, one of these being more significantly populated (60-68%). The AM1 results were not reproduced by the MM2 method, which predicted four low energy conformations. An interesting common feature of 1,2, and 3 that was noted with both methods was the restricted interconversion route from the conformational state to another through rotations about the C(12)—C(13) bond. The conformational results were discussed in terms of a working hypothesis for regulation of relative p. and « analgesic activities of benzomorphans.
Alexandros Makriyannis - One of the best experts on this subject based on the ideXlab platform.
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Conformational preferences of the kappa-selective opioid agonist U50488. A combined molecular mechanics and nuclear magnetic resonance study.
Journal of medicinal chemistry, 1992Co-Authors: Mark Froimowitz, Christine M. Dimeglio, Alexandros MakriyannisAbstract:The conformational preferences of the kappa-selective opioid agonist U50488 have been studied using MM2-87 calculations and nuclear magnetic resonance (NMR) spectroscopy. The calculations were performed for the protonated form with a dielectric constant of 80 and the unprotonated form with dielectric constants of 1.5 and 80. A systematic search found 72 stable conformers with certain consistent conformational preferences for some of the important dihedral angles. The preferred conformers proved to be compact structures stabilized by intramolecular attractive van der Waals interactions, though at least some of these appear to be electrostatically unfavorable. The conformation of U50488 was also examined in aqueous solution using one-dimensional (1D) and two-dimensional (2D) high-resolution 1H NMR techniques such as the interpretation of 1H-1H vicinal coupling constants, 1D and 2D nuclear Overhauser effect (NOE) experiments, and 2D correlated spectroscopy (COSY) experiments. Five crystallographic conformations were examined as well. There was generally good agreement between all three methods of conformational analysis. There appeared to be a reasonable geometrical agreement between the relatively rigid kappa-agonist (-)-Ketazocine and a gauche conformer of U50488. The proposed pharmacophore is also consistent with other kappa-selective analogs of U50488 including one in which the peptide bond is incorporated into a lactam ring. The low affinity of U50488 for mu-receptors was attributed to its cyclohexane ring which occupies space not present in the nonselective (-)-Ketazocine.
Mark Froimowitz - One of the best experts on this subject based on the ideXlab platform.
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Conformational preferences of the kappa-selective opioid agonist U50488. A combined molecular mechanics and nuclear magnetic resonance study.
Journal of medicinal chemistry, 1992Co-Authors: Mark Froimowitz, Christine M. Dimeglio, Alexandros MakriyannisAbstract:The conformational preferences of the kappa-selective opioid agonist U50488 have been studied using MM2-87 calculations and nuclear magnetic resonance (NMR) spectroscopy. The calculations were performed for the protonated form with a dielectric constant of 80 and the unprotonated form with dielectric constants of 1.5 and 80. A systematic search found 72 stable conformers with certain consistent conformational preferences for some of the important dihedral angles. The preferred conformers proved to be compact structures stabilized by intramolecular attractive van der Waals interactions, though at least some of these appear to be electrostatically unfavorable. The conformation of U50488 was also examined in aqueous solution using one-dimensional (1D) and two-dimensional (2D) high-resolution 1H NMR techniques such as the interpretation of 1H-1H vicinal coupling constants, 1D and 2D nuclear Overhauser effect (NOE) experiments, and 2D correlated spectroscopy (COSY) experiments. Five crystallographic conformations were examined as well. There was generally good agreement between all three methods of conformational analysis. There appeared to be a reasonable geometrical agreement between the relatively rigid kappa-agonist (-)-Ketazocine and a gauche conformer of U50488. The proposed pharmacophore is also consistent with other kappa-selective analogs of U50488 including one in which the peptide bond is incorporated into a lactam ring. The low affinity of U50488 for mu-receptors was attributed to its cyclohexane ring which occupies space not present in the nonselective (-)-Ketazocine.
