BU72
Identifiers
  • (2R,3S,3aR,5aR,6R,11bR,11cS)-3a-methoxy-3,14-dimethyl-2-phenyl-2,3,3a,6,7,11c-hexahydro-1H-6,11b-(epiminoethano)-3,5a-methanonaphtho[2,1-g]indol-10-ol
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
PDB ligand
Chemical and physical data
FormulaC28H32N2O2
Molar mass428.576 g·mol−1
3D model (JSmol)
  • CO[C@]12C=C[C@]34C[C@@]1(C)[C@H](N[C@H]2[C@@]35CCN(C)[C@@H]4Cc6ccc(O)cc56)c7ccccc7
  • InChI=InChI=1S/C28H32N2O2/c1-25-17-26-11-12-28(25,32-3)24(29-23(25)18-7-5-4-6-8-18)27(26)13-14-30(2)22(26)15-19-9-10-20(31)16-21(19)27/h4-12,16,22-24,29,31H,13-15,17H2,1-3H3/t22-,23-,24+,25+,26-,27+,28+/m1/s1
  • Key:RGJHUVJQGAAZLK-GKTFKBBASA-N
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BU72 is an extremely potent opioid, with one of the highest known affinities for the μ-opioid receptor.[1] In animal studies, it was found to be a potent analgesic, with a slow onset and long duration of action, but was not considered suitable to develop for medical use.[2] It was used to produce the first crystal structure of the active μ-opioid receptor,[1] and is now widely used to model the activation process.[3][4][5] The stereochemistry has recently been revised, with the phenyl group in the (R) configuration,[6] which has been accepted by the authors of the crystal structure.[7]

BU72 original proposed structure ((S)-phenyl epimer)

See also

References

  1. ^ a b Huang W, Manglik A, Venkatakrishnan AJ, Laeremans T, Feinberg EN, Sanborn AL, et al. (August 2015). "Structural insights into µ-opioid receptor activation". Nature. 524 (7565): 315–21. Bibcode:2015Natur.524..315H. doi:10.1038/nature14886. PMC 4639397. PMID 26245379.
  2. ^ Neilan CL, Husbands SM, Breeden S, Ko MC, Aceto MD, Lewis JW, et al. (September 2004). "Characterization of the complex morphinan derivative BU72 as a high efficacy, long-lasting mu-opioid receptor agonist". European Journal of Pharmacology. 499 (1–2): 107–16. doi:10.1016/j.ejphar.2004.07.097. PMID 15363957.
  3. ^ Sounier R, Mas C, Steyaert J, Laeremans T, Manglik A, Huang W, et al. (August 2015). "Propagation of conformational changes during μ-opioid receptor activation". Nature. 524 (7565): 375–8. Bibcode:2015Natur.524..375S. doi:10.1038/nature14680. PMC 4820006. PMID 26245377.
  4. ^ Cheng JX, Cheng T, Li WH, Liu GX, Zhu WL, Tang Y (January 2018). "Computational insights into the G-protein-biased activation and inactivation mechanisms of the μ opioid receptor". Acta Pharmacologica Sinica. 39 (1): 154–164. doi:10.1038/aps.2017.158. PMC 5758664. PMID 29188799.
  5. ^ Sena DM, Cong X, Giorgetti A (December 2020). "Ligand based conformational space studies of the μ-opioid receptor". Biochimica et Biophysica Acta (BBA) - General Subjects. 1865 (3): 129838. doi:10.1016/j.bbagen.2020.129838. PMID 33373630. S2CID 229721515.
  6. ^ Munro TA (April 2020). "Revised (β-phenyl) stereochemistry of ultrapotent μ opioid BU72". bioRxiv. doi:10.1101/2020.04.01.020883. S2CID 215551137.
  7. ^ Huang W, Manglik A, Venkatakrishnan AJ, Laeremans T, Feinberg EN, Sanborn AL, et al. (August 2020). "Author Correction: Structural insights into μ-opioid receptor activation". Nature. 584 (7820): E16. doi:10.1038/s41586-020-2542-z. PMID 32724208.


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