BU72

BU72
Identifiers
	IUPAC name (1R,2S,4S,5S,6R,9R,10R)-6-methoxy-5,20-dimethyl-4-phenyl-3,20-diazahexacyclo[8.7.3.15,9.01,9.02,6.012,17]henicosa-7,12(17),13,15-tetraen-15-ol;
CAS Number	173265-76-4;
PubChem CID	137348291;
IUPHAR/BPS	9363;
ChemSpider	9662011;
ChEMBL	ChEMBL321570;
PDB ligand	4VO (PDBe, RCSB PDB);
Chemical and physical data
Formula	C28H32N2O2
Molar mass	428.576 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@@]12C[C@@]34C=C[C@@]1([C@H]([C@@]35CCN([C@@H]4CC6=C5C=C(C=C6)O)C)N[C@H]2C7=CC=CC=C7)OC;
	InChI 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-CLYKQLRXSA-N;

BU72 is an extremely potent opioid, with one of the highest known affinities for the μ-opioid receptor. 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.[1] It was used to produce the first crystal structure of the active μ-opioid receptor,[2] and is now widely used to model the activation process.[3][4][5] The stereochemistry has recently been revised, with a proposal that the phenyl group is actually in the β configuration,[6] which has been accepted by the original authors.[7]

BU72 revised structure (β-phenyl epimer)

References

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.
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. doi:10.1038/nature14886. PMC 4639397. PMID 26245379.
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. doi:10.1038/nature14680. PMC 4820006. PMID 26245377.
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. PMID 29188799.
Sena DM, Cong X, Giorgetti A (December 2020). "Ligand based conformational space studies of the μ-opioid receptor". Biochimica et Biophysica Acta. General Subjects. 1865 (3): 129838. doi:10.1016/j.bbagen.2020.129838. PMID 33373630.
Munro TA (April 2020). "Revised (β-phenyl) stereochemistry of ultrapotent μ opioid BU72". BioRxiv. doi:10.1101/2020.04.01.020883.
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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[1] 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.

[2] 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. doi:10.1038/nature14886. PMC 4639397. PMID 26245379.

[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. 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. 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. General Subjects. 1865 (3): 129838. doi:10.1016/j.bbagen.2020.129838. PMID 33373630.

[6] Munro TA (April 2020). "Revised (β-phenyl) stereochemistry of ultrapotent μ opioid BU72". BioRxiv. doi:10.1101/2020.04.01.020883.

[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.

BU72

See also

References