The Molecular and Crystal Structure of Buprenorphine Hydrochloride, a Morphine Analogue

Kratochvíl, Bohumil; Hušák, M.; Bulej, Petr; Jegorov, Alexandr

doi:10.1135/cccc19942472

Cited by 8 publications

(9 citation statements)

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“…Table 2 reports the geometric parameters for the N-substituents of pentazocine and buprenorphine. It can be seen that the calculated values are consistent with experimental data, [27][28][29][30][31] showing only slight deviations.…”

Section: Resultssupporting

confidence: 77%

“…Calculated dihedral angles are consistent with those experimentally determined, [27][28][29][30][31] with no significant deviations to influence the adopted conformation by the pharmacophore.…”

Section: Resultssupporting

confidence: 74%

“…Table 1 reports the distances and dihedrals obtained for the pharmacophore at the B3LYP/6-31+G(d) level of theory and the reported experimental distances obtained by X-ray crystallography. [27][28][29][30][31] Most of the estimated bond lengths are slightly larger than the experimental distances, with deviations of the order of 0.010 Å, which are not significant. The theoretical model used reproduces satisfactorily the geometry of the studied molecules.…”

Section: Resultsmentioning

confidence: 99%

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Molecular Modeling Study on Morphine Derivatives Using Density Functional Methods and Molecular Descriptors

2010

Journal of the Korean Chemical Society

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ABSTRACT. Computational studies were carried out on the opiates morphine, heroin, codeine, pentazocine, and buprenorphine, under the density functional theory. The geometric parameters of the pharmacophore and substituents were evaluated at the B3LYP/6-31+G(d) level of theory. The electronic structure calculations were performed using the same hybrid functional at the B3LYP/6-311++G (d,p) level of theory . The atomic charges were obtained by Mulliken population analysis. Given the reported biological activity, calculated partition coefficients, and electronic and geometric analysis, pentazocine and buprenorphine were chosen as models for proposed analogues. These analogues were then studied and compared with the model molecules. The study reveals that the geometry and electronic structure of the pharmacophore remains consistent in the presence of different substituents. Because the proposed analogues preserve the studied properties of the model molecules, it is likely that these analogues display biological activity.

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Section: Resultssupporting

confidence: 77%

Section: Resultssupporting

confidence: 74%

Section: Resultsmentioning

confidence: 99%

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Molecular Modeling Study on Morphine Derivatives Using Density Functional Methods and Molecular Descriptors

2010

Journal of the Korean Chemical Society

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“…Within this study, we investigate the docking properties of twelve non-peptide non-endogenous opioid agonists and antagonists ( Fig. 1; Beta-Funaltrexamine [13]; Bremazocine [14]; Buprenorphine [15]; Diprenorphine, Etorphine, Fentanyl [16]; Morphine [17]; Naloxone [18]; Naltrexone [19]; Nor-binaltorphimine [20]; Oxymorphone [21]; U-69,593 [22]) on the backbone crystal structure (2.8 Angstroms) of the mouse MOR in the monomer configuration [2].…”

Section: Non-peptide Ligands and Receptormentioning

confidence: 99%

A Structural Feature of the Non-Peptide Ligand Interactions with Mice Mu-Opioid Receptors

Noori

Mücksch

Urbassek³

2015

CAD

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By binding to and activating the G-protein coupled μ-, κ- and δ-opioid receptors in the central nervous system, opiates are known to induce analgesic and sedative effects. In particular, non-peptide opioid ligands are often used in clinical applications to induce these therapeutically beneficial effects, due to their superior pharmacokinetics and bioavailability in comparison to endogenous neuropeptides. However, since opioid alkaloids are highly addictive substances, it is necessary to understand the exact mechanisms of their actions, specifically the ligand-binding properties of the target receptors, in order to safely apply opiates for therapeutic purposes. Using an in silico molecular docking approach (AutoDock Vina) combined with two-step cluster analysis, we have computationally obtained the docking scores and the ligand-binding pockets of twelve representative non-peptide nonendogenous agonists and antagonists at the crystallographically identified μ-opioid receptor. Our study predicts the existence of two main binding sites that are congruently present in all opioid receptor types. Interestingly, in terms of the agonist or antagonist properties of the substances on the receptors, the clustering analysis suggests a relationship with the position of the ligand-binding pockets, particularly its depth within the receptor structure. Furthermore, the binding affinity of the substances is directly correlated to the proximity of the binding pockets to the extracellular space. In conclusion, the results provide further insights into the structural features of the functional pharmacology of opioid receptors, suggesting the importance of the binding position of non-peptide agonists and antagonists- specifically the distance and the level of exposure to the extracellular space- to their dissociation kinetics and subsequent potency.

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“…The C(6)-C (14) ethano bridge of the originally boatshaped ring forms the fused cage, but it is distorted from ideal construction due to the new formed three-membered ring. The hydroxyl oxygen, O(1), is coplanar with O(2), C(6) and C(22), and the methyl group, C(23), oriented inversely against the morphine ethanyl bridge.…”

Section: Resultsmentioning

confidence: 99%

Study on Synthesis of Thebaine Derivatives

Li¹,

Liu²,

Wu³

et al. 2005

Chin. J. Chem.

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The reaction of 7α-acetyl-6,14-endoethano-6,7,8,14-tetrahydrothebaine with 2-(thien-2-yl)ethylmagnesium bromide was investigated. The tertiary alcohol derivative 7α-[R-1-hydroxyl-1-methyl-3-(thien-2-yl)propyl])-6,14endoethano-6,7,8,14-tetrahydrothebaine (3) and a by-product 4 were isolated. The structure of 4 was elucidated by X-ray analysis. The Grignard reaction shows high degree of stereoselectivity according with Cram rule. The crystal structure of 4 indicates that dihydrofuran ring was opened to form a phenolic hydroxyl group and a three-membered ring structure. It maintains the main rigid structure of morphine and contains a C(6)-C(14) enthano bridge. The 1-hydroxyl-1-methyl-3-(thien-2-yl)propyl group at C(7) position adopted S-configuration.

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The Molecular and Crystal Structure of Buprenorphine Hydrochloride, a Morphine Analogue

Cited by 8 publications

References 0 publications

Molecular Modeling Study on Morphine Derivatives Using Density Functional Methods and Molecular Descriptors

Molecular Modeling Study on Morphine Derivatives Using Density Functional Methods and Molecular Descriptors

A Structural Feature of the Non-Peptide Ligand Interactions with Mice Mu-Opioid Receptors

Study on Synthesis of Thebaine Derivatives

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