SR-14968

SR-14968
Identifiers
	IUPAC name 3-[1-[1-(4-bromophenyl)ethyl]piperidin-4-yl]-5,6-dichloro-1H-benzimidazol-2-one;
CAS Number	2133455-40-8;
PubChem CID	130431386;
ChemSpider	95781537;
Chemical and physical data
Formula	C20H20BrCl2N3O
Molar mass	469.20 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C1=CC=C(C=C1)Br)N2CCC(CC2)N3C4=CC(=C(C=C4NC3=O)Cl)Cl;
	InChI InChI=1S/C20H20BrCl2N3O/c1-12(13-2-4-14(21)5-3-13)25-8-6-15(7-9-25)26-19-11-17(23)16(22)10-18(19)24-20(26)27/h2-5,10-12,15H,6-9H2,1H3,(H,24,27); Key:DJSSLECNUQMYKG-UHFFFAOYSA-N;

SR-14968 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. It is closely related to other compounds such as brorphine and SR-17018. Similarly to brorphine, SR-14968 shows robust biased agonist activity in vitro, but in animal studies in vivo behaves more like a typical opioid agonist at higher dose ranges, though still with a superior safety profile compared to unbiased agonists such as fentanyl. Compounds of this class are under development as potential analgesic medications with lower risk of overdose and drug dependence compared to traditional opioid drugs.^[1]^[2]^[3]^[4]^[5]

References

^ Schmid CL, Kennedy NM, Ross NC, Lovell KM, Yue Z, Morgenweck J, et al. (November 2017). "Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics". Cell. 171 (5): 1165–1175.e13. doi:10.1016/j.cell.2017.10.035. PMC 5731250. PMID 29149605.
^ Schwienteck KL, Faunce KE, Rice KC, Obeng S, Zhang Y, Blough BE, et al. (May 2019). "Effectiveness comparisons of G-protein biased and unbiased mu opioid receptor ligands in warm water tail-withdrawal and drug discrimination in male and female rats". Neuropharmacology. 150: 200–209. doi:10.1016/j.neuropharm.2019.01.020. PMC 6476319. PMID 30660628.
^ Stahl EL, Schmid CL, Acevedo-Canabal A, Read C, Grim TW, Kennedy NM, et al. (November 2021). "G protein signaling-biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists". Proceedings of the National Academy of Sciences of the United States of America. 118 (48). Bibcode:2021PNAS..11802178S. doi:10.1073/pnas.2102178118. PMC 8640941. PMID 34819362.
^ Kudla L, Bugno R, Podlewska S, Szumiec L, Wiktorowska L, Bojarski AJ, Przewlocki R (December 2021). "Comparison of an Addictive Potential of μ-Opioid Receptor Agonists with G Protein Bias: Behavioral and Molecular Modeling Studies". Pharmaceutics. 14 (1): 55. doi:10.3390/pharmaceutics14010055. PMC 8779292. PMID 35056950.
^ Noble F, Marie N (2021). "Biased Opioid Ligands: Revolution or Evolution?". Frontiers in Pain Research. 2. Lausanne, Switzerland: 722820. doi:10.3389/fpain.2021.722820. PMC 8915667. PMID 35295469.

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[1] Schmid CL, Kennedy NM, Ross NC, Lovell KM, Yue Z, Morgenweck J, et al. (November 2017). "Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics". Cell. 171 (5): 1165–1175.e13. doi:10.1016/j.cell.2017.10.035. PMC 5731250. PMID 29149605.

[2] Schwienteck KL, Faunce KE, Rice KC, Obeng S, Zhang Y, Blough BE, et al. (May 2019). "Effectiveness comparisons of G-protein biased and unbiased mu opioid receptor ligands in warm water tail-withdrawal and drug discrimination in male and female rats". Neuropharmacology. 150: 200–209. doi:10.1016/j.neuropharm.2019.01.020. PMC 6476319. PMID 30660628.

[3] Stahl EL, Schmid CL, Acevedo-Canabal A, Read C, Grim TW, Kennedy NM, et al. (November 2021). "G protein signaling-biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists". Proceedings of the National Academy of Sciences of the United States of America. 118 (48). Bibcode:2021PNAS..11802178S. doi:10.1073/pnas.2102178118. PMC 8640941. PMID 34819362.

[4] Kudla L, Bugno R, Podlewska S, Szumiec L, Wiktorowska L, Bojarski AJ, Przewlocki R (December 2021). "Comparison of an Addictive Potential of μ-Opioid Receptor Agonists with G Protein Bias: Behavioral and Molecular Modeling Studies". Pharmaceutics. 14 (1): 55. doi:10.3390/pharmaceutics14010055. PMC 8779292. PMID 35056950.

[pmid35295469-5] Noble F, Marie N (2021). "Biased Opioid Ligands: Revolution or Evolution?". Frontiers in Pain Research. 2. Lausanne, Switzerland: 722820. doi:10.3389/fpain.2021.722820. PMC 8915667. PMID 35295469.

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See also

References