BU72   Click here for help

GtoPdb Ligand ID: 9363

Synonyms: compound 10 (Husbands and Lewis, 1995) [4]
PDB Ligand
Compound class: Synthetic organic
Comment: BU72 was reported as a long-lasting μ receptor agonist [5]. Its very high affinity meant that it was not considered as a clinical candidate. Strong lipophilic binding interactions with the μ receptor confer slow receptor kinetics, and therefore long duration of action.
We revised the chemical structure in March 2021, based on data arising from analysis of the crystal structure of the BU72/μ receptor complex that was deposited to the Protein Data Bank (5C1M) [2-3]. This shows that the (β-phenyl) group of BU72 shoud be in the (R) configuration. BU72 has been used in a number of studies to model the μ receptor activation process [1,6].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 2
Rotatable bonds 2
Topological polar surface area 44.73
Molecular weight 428.25
XLogP 3.03
No. Lipinski's rules broken 0
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Canonical SMILES CO[C@@]12C=C[C@@]34[C@@]5([C@@H]1N[C@@H]([C@]2(C)C3)c1ccccc1)CCN([C@@H]4Cc1c5cc(O)cc1)C
Isomeric SMILES CO[C@@]12C=C[C@@]34[C@@]5([C@@H]1N[C@@H]([C@]2(C)C3)c1ccccc1)CCN([C@@H]4Cc1c5cc(O)cc1)C
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
1. Cheng JX, Cheng T, Li WH, Liu GX, Zhu WL, Tang Y. (2018)
Computational insights into the G-protein-biased activation and inactivation mechanisms of the μ opioid receptor.
Acta Pharmacol Sin, 39 (1): 154-164. [PMID:29188799]
2. Huang W, Manglik A, Venkatakrishnan AJ, Laeremans T, Feinberg EN, Sanborn AL, Kato HE, Livingston KE, Thorsen TS, Kling RC et al.. (2015)
Structural insights into µ-opioid receptor activation.
Nature, 524 (7565): 315-21. [PMID:26245379]
3. Huang W, Manglik A, Venkatakrishnan AJ, Laeremans T, Feinberg EN, Sanborn AL, Kato HE, Livingston KE, Thorsen TS, Kling RC et al.. (2020)
Author Correction: Structural insights into μ-opioid receptor activation.
Nature, 584 (7820): E16. [PMID:32724208]
4. Husbands SM, Lewis JW. (1995)
Morphinan cyclic imines and pyrrolidines containing a constrained phenyl group: high affinity opioid agonists.
Bioorg Med Chem Lett, 5: 2969–2974.
5. Neilan CL, Husbands SM, Breeden S, Ko MC, Aceto MD, Lewis JW, Woods JH, Traynor JR. (2004)
Characterization of the complex morphinan derivative BU72 as a high efficacy, long-lasting mu-opioid receptor agonist.
Eur J Pharmacol, 499: 107-16. [PMID:15363957]
6. Sena Jr DM, Cong X, Giorgetti A. (2021)
Ligand based conformational space studies of the μ-opioid receptor.
Biochim Biophys Acta Gen Subj, 1865 (3): 129838. [PMID:33373630]