SR-17018

SR-17018
Identifiers
IUPAC name
  • 5,6-dichloro-3-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-1H-benzimidazol-2-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC19H18Cl3N3O
Molar mass410.72 g·mol−1
3D model (JSmol)
SMILES
  • C1CN(CCC1N2C3=CC(=C(C=C3NC2=O)Cl)Cl)CC4=CC=C(C=C4)Cl
InChI
  • InChI=1S/C19H18Cl3N3O/c20-13-3-1-12(2-4-13)11-24-7-5-14(6-8-24)25-18-10-16(22)15(21)9-17(18)23-19(25)26/h1-4,9-10,14H,5-8,11H2,(H,23,26)
  • Key:LAGUDYUGRSQDKS-UHFFFAOYSA-N

SR-17018 is a drug which acts as a biased agonist at the μ-opioid receptor, selective for activation of the G-protein signalling pathway over β-arrestin 2 recruitment.[1] In animal studies it produces analgesic effects but with less respiratory depression and development of tolerance than conventional opioids.[2][3][4][5] SR-17018 is also a noncompetitive opioid agonist.[6] It produces very little hyperactivity in mice, does not induce locomotor sensitization and counteracts the hyperactivity produced by morphine.[7]

See also

References

  1. ↑ Schmid CL, Kennedy NM, Ross NC, Lovell KM, Yue Z, Morgenweck J, Cameron MD, Bannister TD, Bohn LM (November 2017). "Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics". Cell. 171 (5): 1165–75.e13. doi:10.1016/j.cell.2017.10.035. PMC 5731250. PMID 29149605.
  2. ↑ Grim TW, Schmid CL, Stahl EL, Pantouli F, Ho JH, Acevedo-Canabal A, et al. (January 2020). "A G protein signaling-biased agonist at the μ-opioid receptor reverses morphine tolerance while preventing morphine withdrawal". Neuropsychopharmacology. 45 (2): 416–425. doi:10.1038/s41386-019-0491-8. PMC 6901606. PMID 31443104.
  3. ↑ Grim TW, Acevedo-Canabal A, Bohn LM (January 2020). "Toward Directing Opioid Receptor Signaling to Refine Opioid Therapeutics". Biol Psychiatry. 87 (1): 15–21. doi:10.1016/j.biopsych.2019.10.020. PMC 6919561. PMID 31806082.
  4. ↑ Podlewska S, Bugno R, Kudla L, Bojarski AJ, Przewlocki R (October 2020). "Molecular Modeling of µ Opioid Receptor Ligands with Various Functional Properties: PZM21, SR-17018, Morphine, and Fentanyl-Simulated Interaction Patterns Confronted with Experimental Data". Molecules. 25 (20): 4636. doi:10.3390/molecules25204636. PMC 7594085. PMID 33053718.
  5. ↑ Pantouli F, Grim TW, Schmid CL, Acevedo-Canabal A, Kennedy NM, Cameron MD, et al. (December 2020). "Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain". Neuropharmacology. 185 108439. doi:10.1016/j.neuropharm.2020.108439. PMC 7887086. PMID 33345829. S2CID 229306872.
  6. ↑ Stahl EL, Schmid CL, Acevedo-Canabal A, Read C, Grim TW, Kennedy NM, Bannister TD, Bohn LM (November 2021). "G protein signaling-biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists". Proc Natl Acad Sci U S A. 118 (48) e2102178118. Bibcode:2021PNAS..11802178S. doi:10.1073/pnas.2102178118. PMC 8640941. PMID 34819362.
  7. ↑ Acevedo-Canabal A, Grim TW, Schmid CL, McFague N, Stahl EL, Kennedy NM, Bannister TD, Bohn LM (June 2023). "Hyperactivity in Mice Induced by Opioid Agonists with Partial Intrinsic Efficacy and Biased Agonism Administered Alone and in Combination with Morphine". Biomolecules. 13 (6) 935. doi:10.3390/biom13060935. PMC 10295947. PMID 37371516.
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